Spike activity and histofluorescence correlated in the giant dopamine neurone of Planorbis corneus. The relationship between catecholamine fluorescence and electrical activity of the nerve cell has been investigated in the giant dopamine neuron (GDN) of the left pedal ganglion of the European water snail, Planorbis corneus. Electrical recordings were performed in vitro with intracellular microelectrodes on 35 GDN. The ganglion was frozen to -195 degrees C with the electrode in situ and processed for histochemical microfluorimetry. The intensity of catecholamine fluorescence was measured over different places (42/cell) throughout the cytoplasm of the GDN. In order to investigate the temporal relation between histochemical and electrophysiological parameters, the activity of 21 GDN was changed by administration of nicotine to the bathing solution (10(-5)--10(-7) M). This treatment was followed by depolarization in most of the GDN, with increased firing in two thirds and decreased activity in one third of the spontaneously active cells, whereas hyperpolarization was seen in 4 GDN, accompanied by a decrease in firing. Acetylcholine (10(-5) M) tested on one GDN caused depolarization and increased firing. A signigicant positive correlation was found between the fluorescence intensity of individual GDN and the firing rate of these cells as observed during the last 60 sec or the last 10 sec before freezing. The correlation coefficient dropped markedly when the first rates of the 2nd, 3rd, or 4th and 5th min before freezing were correlated with cellular fluorescence intensity. Intensity was not correlated with the resting membrane potential recorded at the time of freezing. The intensity response to activation was not uniform throughout the cytoplasm of GDN. Neurons with increased mean fluorescence intensity regularly showed small clusters and cristae of intensely fluorescent material surrounded by less fluorescent parts of the cytoplasm. This morphological observation of increased intensity differences between cytoplasmic structures was confirmed by the statistics of the intensity values determined in individual cells. The present observations demonstrate the existence of a relation between cell firing and neuronal dopamine fluorescence at the level of the individual nerve cell. The activity immediately preceding the time of freezing of the cell appears to be most important. Certain components of the cytoplasm appear to react preferentially; their subcellular nature remains to be elucidated. The link between electrical activity and cellular dopamine fluorescene was found to be basically the same in the giatn invertebrate neuron and in the dopamine nerve cells of rat substantia nigra.


Three-dimensional organization of the endoplasmic reticulum in supraoptic neurons of the rat. A structural functional correlation. Double impregnation staining of tissue was used to study on thick sections the three-dimensional configuration of the peripheral endoplasmic reticulum in neurosecretory neurons of the supraoptic nucleus in control and water-deprived rats. According to the spatial organization of the endoplasmic reticulum, two types of neurons are described in this report: Type I neurons which predominated in control rats (70%) exhibited characteristically large lamellar structures connected to loosely anastomosed tubules. In type II neurons, which prevailed in water-deprived rats (85%) the endoplasmic reticulum had the appearance of a highly-developed network of interconnected tubules, with no lamellar structures. Double impregnation staining combined with high resolution radioautography after [3H]leucine administration showed that the tubular configuration of the endoplasmic reticulum was the main active site of protein synthesis by contrast with the lamellar components, whose activity seemed poor. In terms of protein synthesis, the three-dimensional configuration of the peripheral endoplasmic reticulum of the supraoptic neurons appeared therefore to be closely connected with their functional state.


Influence of carotid and aortic baroreceptors on neurosecretory neurons in supraoptic nuclei. (1) The effects of arterial baroreceptor stimulation on the activity of 'identified' neurosecretory cells in supraoptic nuclei (SON) of the hypothalamus were investigated in anesthetized cats. (2) Stimulation of baroreceptors by distension of an 'isolated' carotid sinus greatly inhibited SON activity. A linear relationship was found to exist between stimulus intensity (an increase in the sinus pressure) and the degree of inhibition of SON neuron activity. This inhibitory effect was abolished by section of the sinus nerve. (3) The inhibitory effect of baroreceptors on SON neuron activity was most pronounced in the first 5 sec during stimulation, and the effect became less when the stimulus lasted for a long period. At the end of stimulation there was a transient reversal of the response. (4) The excitation of aortic baroreceptors by occluding descending aorta strongly inhibited SON neuron activity. (5) Occlusion of carotid arteries augmented the SON neuron activity. Electrical stimulation of the sinus nerve caused an excitation or an inhibition of SON neurons, depending on the stimulus intensities. Apparently these stimuli produced different degrees of excitation in baro- and chemoreceptors. (6) Combination of chemo- and baroreceptor stimulations revealed that the excitatory effect exerted by chemoreceptor stimulation on SON neurons was reversed or blocked by baroreceptor activation, indicating the powerful inhibitory influence of baroreceptors.


GABA-accumulating neurons in the nucleus raphe dorsalis and periaqueductal gray in the rat: a biochemical and radioautographic study. The possibility of a GABAergic innervation of the nucleus raphe dorsalis (NRD) has been investigated by using the following approaches: (i) the identification of the principal neuronal groups afferent to the NDR by using horseradish peroxidase retrograde transport, (ii) the determination of glutamate decarboxylase activity (GAD) in the NRD after lesioning these groups or their putative pathways, and (iii) the radioautographic identification of terminals axons and nerve cells accumulating intraventricularly injected [3H]GABA. The hypothesis of a local GABAergic network is supported by the failure to obtain important changes in GAD after lesions of NRD afferents and the presence in this nucleus of terminals, fibers and nerve cell bodies  accumulating [3H]GABA. It appears that these GABA-accumulating neurons could represent a portion of aperiventricular GABAergic system in the periaqueductal gray and the pontine ventricular gray.


Brain sodium uptake after choroid plexectomy. When in a (control) series of rats brain sodium uptake (BSU) -- as calculated from estimated radioactivities of brain and blood following the injection of [24Na]sodium chloride 30 min and [22Na]sodium chloride one minute before killing -- was plotted against average arterial blood pressure of the animals during the 30 min survival period, a linear dependence of BSU on blood pressure was observed. In another series of animals, in which the choroid plexuses of the fourth and both lateral ventricles had been removed, the regression line showed the same slope, but a significantly lower intercept. On the other hand, a series of rats which had been subjected to a sham operation without removal of the choroid plexuses, showed a regression line not different from the control series. The results indicate that probably the blood pressure independent component of brain sodium uptake, as represented by the intercept of the regression line, for the greater part constitutes cerebrospinal fluid secretion by the choroid plexus.


Projections to the neostriatum from the cat precruciate cortex. Anatomy and physiology. The projections to the striatum from two cytoarchitectonically and functionally distinct subdivisions of the cat precruciate motor cortex were studied using anatomical and electrophysiological techniques. Our results indicate that the medial precruciate cortex (stimulation of which leads to movements of the axial and proximal musculature) has a widespread projection to the lateral half of the caudate nucleus. The lateral precruciate cortex (stimulation of which leads to movements of the distal musculature) has a localized projection within the caudate nucleus adjacent to the internal capsule. Both medial and lateral precruciate areas project to the putamen. These results are discussed in relation to recent studies suggesting that the basal ganglia are involved in the enabling and sequencing of movements.


Functional reinnervation of rat hippocampus by locus coeruleus implants. Transplants of the embryonic locus coeruleus (LC) region were implanted into the circuity of the hippocampal formation in adult rats in which the normal adrenergic afferents to the hippocampus had been removed. The growth of new adrenergic axons from the implant in the denervated hippocampus was followed for 1-14 months after surgery by means of fluorescence histochemistry, and the function of the implant-hippocampal connections was tested electrophysiologically after 2-3 months survival. In the successful cases the entire hippocampal formation was reinnervated from the LC implant within 3-6 months after operation, and the newly formed innervation still persisted unchanged by 14 months. The reinnervation was equally effective irrespective of the route by which the axons entered the hippocampus, i.e. along the lesioned fornix-fimbria or along a retrosplenial route. The pattern formed by the ingrowing LC axons mimicked to a large extent that of the normal LC afferents. Little growth was seen into denervated terminal fields of the commissural, septal or entorhinal afferents, pointing to a preference of the ingrowing LC fibers for the areas normally innervated by adrenergic afferents. In the electrophysiological experiments, stimulation of the LC implants caused (in 20 out of 29 cells monitored) an inhibition of the spontaneous activity of neurons in the host hippocampus. This inhibition had a relatively long latency and a long duration, similar to that observed after stimulation of the innate LC in the intact rat. As in the normal rat, the inhibitory responses were blocked by systemic or local application of the beta-adrenergic receptor blockers propranolol or sotalol. It is concluded that the adult rat brain is capable of carrying out all steps involved in correct functional reinnervation of a denervated region. Moreover, the implant-hippocampal preparation should be a highly suitable model system for functional studies of a central noradrenergic connection.


The specificity of reactive synaptogenesis: a comparative study in the adult rat hippocampal formation. The CA1 region of the hippocampus in the mature rat is shown to possess the capacity to form new synapses following a lesion of either the commissural afferents, which removes 41% of the synaptic input to stratum radiatum, or commissural and associational afferents, which destroys 74% of the synaptic input. With both types of lesion, extensive reinnervation occurs without obvious changes in lamination of afferent fibers and without accompanying changes in the acetylcholinesterase-(AChE) staining pattern. This is in contrast to what is known to occur in the hippocampal dentate gyrus following an ipsilateral entorhinal lesion where afferent lamination is reordered and where AChE-staining intensifies. A comparison between the disparate patterns of reinnervation in these closely related structures affords the opportunity to examine some of the specific factors that may regulate synaptic readjustments in brain.


Morphological identification and biochemical characterization of isolated brain cell nuclei from the developing rat cerebellum. Cell nuclei from developing rat cerebellum were isolated and the various types of nuclei were characterized and quantified. Nuclear pellets appeared to be both quantitatively and qualitatively representative of the entire cerebellum, and of sufficient purity to perform biochemical studies as well as morphological comparison with histological sections. Isolated nuclei were classified into 6 groups based on nuclear size and shape, heterochromatin aggregations, and nucleoplasmic density. The total population of cerebellar cells primarily consisted of two types of nuclei after day 10. One group of nuclei, resembling those of internal granule neurons or external germinal cells, contributed at least 70% of the total isolated cell nuclei from day 1 to day 90, whereas another nuclear group that was identified as dark oligodendrocytes constituted 8-9% of the total population on days 45 and 90. Nuclear DNA, RNA, and protein content of the cerebellum also were determined throughout postnatal development. DNA concentration markedly declined after day 15, while the RNA/DNA ratio increased until day 3 and remained constant to day 90. The nuclear protein/DNA ratio increased from birth to day 3, decreased to its lowest value on day 10, and increased to day 90. Utilizing DNA values, the total cell population as well as contributions of different cell types were calculated. At birth the cerebellum was estimated to contain 5.9 million cells, increasing to 94 million by day 21. By day 90, 107 million cells were present, of which 8.6 million oligodendrocytes and 93.6 million internal granule cells were estimated.


Central gray and medial hypothalamic stimulation: correlation between escape behavior and unit activity. A chronic experiment and an acute one were carried out in the same rat in order to get information on the neuronal events correlated with the escape latency (EL) induced by an electrical stimulation in the mesencephalic central gray (CG) or in the medial hypothalamus (MH). Escape latencies as well as unitary MH and CG neuronal responses (104 units in 25 rats) were studied as functions of the intensity and the pulse duration of a 50 pulses/sec stimulation train. The CG and/or the MH neuronal firing rate was either synchronized or diffusely altered, either inhibited or activated, by the CG or the MH stimulations. Many neuronal firing rate alterations were highly correlated with the escape speed (ES = 1/EL) induced by the same stimulation. Intensity duration trade-off functions were computed from both the EL and the unit recordings. Chronaxie determinations were performed from these data: the behaviorally determined chronaxies did not differ from the unitary ones (limit values: 0.05-0.42 msec). The discussion bear on the possible role of the observed neuronal alterations induced by CG or MH stimulations in relation to their behavioral effects.


Catecholamines and convulsions.

Catecholamines and convulsions. Severe depletion of brain noradrenaline and separately of brain dopamine was induced in rats by intracerebral injection of the selective neurotoxin 6-hydroxydopamine, and the susceptibility of the treated animals to various seizure-inducing manipulations was examined. A significant potentiation of the seizures induced both by Metrazol and by electroconvulsive shock was found in animals depleted of brain noradrenaline, but no alteration was seen after depletion of brain dopamine on either measure. The catecholaminergic drug cocaine also induced seizures, but these were found not to depend on either brain noradrenaline or dopamine as they continued to occur in the virtual absence of either catecholamine. It is concluded that cocaine induces seizures by a non-specific toxic mechanism and that noradrenaline, but not dopamine, is involved in reducing the suceptibility of the central nervous system to the several distinct forms of seizure induction examined.


The effect of hyperglycemia on brain capillary permeability in the lizard, Anolis carolinensis. A freeze-fracture analysis of blood-brain barrier pathology. The anatomical basis of the blood-brain barrier in the American chameleon, Anolis carolinensis, is the system of tight intercellular junctions that occurs between apposed endothelial cells of brain capillaries. Under normal physiological conditions, capillaries in the brain cortex of these animals remain sealed by interendothelial zonulae occludentes and, consequently, escape of exogenous tracer proteins such as horseradish peroxidase (HRP) into the extracellular compartment of the central nervous system is prevented. Systemic injection of 2.7 mg of D-glucose into chameleons results in increased brain capillary permeability, as evidenced by escape of HRP or Trypan blue into the intercellular spaces of central neuropil. Freeze-fracture analysis of brain capillary endothelia of glucose-hyperglycemic lizards revealed no alteration of the ridge and groove construction of endothelial tight junctions, indicating that although the blood-brain interface becomes leaky during severe hyperglycemia, the capillary zonulae occludentes are not affected. Evidence obtained in this study strongly supports the notion that the increased capillary permeability is the result of amplified transendothelial transport. The effect is manifest as and facilitated by the formation of chains of pinocytotic vesicles derived from the luminal surface of the endothelial cells, which fuse to create open trans-endothelial conduits. It is likely that formation of open channels that traverse brain capillary endothelial cells, as a response to hyperglycemia, could allow temporarily unrestricted passage of a wide range of molecules, some potentially toxic, into the CNS extracellular milieu. This is the first report to unequivocally document with freeze-cleave techniques, that abnormally elevated levels of blood sugar can affect blood-brain interface permeability. This finding suggests that similar consequences may be expected to result from diabetic hyperglycemia in humans.


Conditioned aversion to brain-stimulation reward: effects of electrode placement and prior experience. A conditioned aversion to rewarding amygdaloid brain-stimulation was established by injecting rats with toxic doses of 0.15 M LiCl immediately after an initial self-stimulation session. The aversion had extinguished by the third self-stimulation session, 96 h after conditioning. This effect cannot be attributed to general depressant effects of LiCl on self-stimulation as treatment with LiCl 24 h before the second self-stimulation session was ineffective. Furthermore, this conditioned aversion was locus specific as LiCl injections immediately after the first test session had no disruptive effects on self-stimulation in the substantia nigra. The parallels between conditioned aversion to rewarding brain-stimulation in the amygdala and late aversion were strengthened by the fact that the novelty of brain-stimulation reward was an important factor in the conditioning effect. These data have important implications for understanding the sensory properties of brain-stimulation reward.


Experimental hypertension and catecholamine distribution in the rat brain. Hypertension was induced in rats (Hebrew University strain) by three different procedures: (1) deoxycorticosterone acetate (DOCA)--salt treatment; (2) unilateral renal artery clip or (3) chronic salt-loading. Noradrenaline (NA) and dopamine (DA) distribution in different brain areas was assayed following induction of hypertension. NA content increased significantly in various areas: the increase of NA in the pons-medulla was common to all procedures inducing hypertension. NA content increased also in the mesencephalon, the hypothalamus and the rest of the forebrain (DOCA--salt hypertension), in the mesencephalon, the hypothalamus and the cortex (in renal clip hypertension). No significant changes in DA content were observed in any region of the brain following induction of hypertension by the three different methods. In two substrains, selected from the Hebrew University strain, for their respective sensitivity (H) or immunity (N) to hypertension induced by DOCA--salt treatment, there were no significant increases in NA or DA in any part of the brain following DOCA--salt treatment. Comparison of NA concentrations in these strains showed that NA was significantly higher in the pons-medulla of the untreated N strain rats than in the medulla of untreated H strain or in untreated rats of the original strain (Hebrew University). A model is presented suggesting that central NA-containing neurons plays a major role in controlling hypertension.


Responses of substantia nigra neurones to noxious stimulation. Experiments were performed to determine whether substantia nigra neurones respond to noxious stimulation. Some nigral neurones were found to respond to both noxious radiant heat and intra-arterially administered bradykinin. Most nociceptive neurones were excited by noxious stimulation although some exhibited a reduction in firing rate. Following the injection of bradykinin, responses to noxious heat were reduced in magnitude for periods of up to an hour. These results show that some nigral neurones are nociceptive and provide further support for the suggestion that dopamine is involved in nociceptive mechanisms. In addition it is suggested that bradykinin may represent a rather gross of non-specific form of noxious stimulation.


Restoration of corticosteroid periodicity in obese rats by limited a.m. food access. Absence of circadian periodicity of plasma corticosteroid levels has previously been reported to occur in animals maintained under constant light and in animals with suprachiasmatic nuclear lesions. Such animals also exhibit aperiodic rather than normal nocturnal eating. Restricted a.m. access to food (09.30--11.30 h) in such animals results in appearance of circadian corticosteroid periodicity (peak at 08.00 h) similar to that seen in normal animals on a similar food restriction regimen. The present study investigated the nature of adrenal circadian periodicity in obese rats who are reported to exhibit aperiodic feeding. Such aperiodic feeding occurred in obese male, but not in obese female, animals. These obese male animals manifested absent corticosteroid circadian periodicity. Restricted a.m. access to food was associated with the appearance of such periodicity similar to that described above in the two other experimental situations. These studies indicate differences in eating behavior and corticosteroid periodicity between obese male and obese female rats. They provide additional confirmation, in animals under normal light--dark conditions and in the absence of CNS lesions, of the role of periodic feeding in the generation of adrenal circadian periodicity.


The discrete anatomical localization of vagal aortic afferents within a catecholamine-containing cell group in the nucleus solitarius. The centripetal transport of horseradish peroxidase (HRP) was used to visualize the central projections of afferent fibers of the aortic arch nerve to the nucleus solitarius in pigeons. Our results indicate that aortic nerve afferents have a restricted distribution within one subdivision of the nucleus solitarius, designated the subnucleus sulcalis dorsalis. Histofluorescence studies revealed that the aortic nerve projection area is extremely rich in catecholamine-containing neurons.


Retinal ganglion cell response to axotomy and nerve growth factor in the regenerating visual system of the newt (Notophthalmus viridescens): an ultrastructural morphometric analysis. Nerve growth factor (NGF) treatment, given as a single 200 BU intraocular injection at the time of optic nerve transection, was found to significantly accelerate the retinal ganglion cell response to axotomy in the newt (Notophthalmus viridescens). In the control series the per cent of neurons in the retinal ganglion layer demonstrating nuclear reactivity (i.e. chromatin changes) reaches a peak by 14 days post axotomy (14 DPA), plateaus through 21 DPA and falls thereafter, returning to control levels by 90 DPA. NGF treatment is shown to significantly accelerate the entrance of responding retinal ganglion cells into the reactive nuclear phase between 1 and 7 DPA, and by 7 DPA nuclear reactivity has reached a peak, in contrast to 14 DPA for control values. Consequently, NGF treatment causes retinal ganglion cells to be in the nuclear reactive state a week longer than controls but reactivity diminishes after 21 DPA as in controls. Electron microscopic morphometric analysis further substantiates these observations by demonstrating that NGF treatment can elicit certain cellular organelle changes a week earlier (i.e. at 7 DPA) than they would normally occur (i.e. at 14 DPA) in response to axotomy. In addition to eliciting cellular hypertrophy at 7 DPA, NGF treatment significantly increases Golgi field densities in the neuronal perikaryal cytoplasm as well as a doubling of the number of nucleoli per nucleus and stimulating a significant increase in nucleolar cross-sectional areas. A dose-response relationship exists between the per cent of retinal ganglion cells demonstrating nuclear reactivity at 7 DPA and various NGF concentrations which compares favorably with the dose response study involving the number of regenerating axons per nerve cross-section at 14 DPA. Studies to determine if the NGF mediated responses were a specific effect elicited by this protein molecule or whether they are also produced by other peptides which share some properties in common with NGF demonstrate that only NGF is capable of eliciting these responses.


Neurochemical and morphological studies of bulk isolated rat brain cells. II. Preparation of viable cerebral neurons which retain synaptic complexes. The bulk isolation from rat cerebral cortex of viable neurons retaining synaptic complexes is described. The basis of this procedure is to dissociate the neurons in situ from the surrounding glial cells. The glial structures that are normally adjacent to the neuronal cell body and to the proximal parts of the neuronal processes are largely destroyed by perfusion of the brain under special conditions. The most important of these conditions was found to be a hyperosmolar concentration of hexoses in the perfusion medium. In addition, the presence of collagenase and hyaluronidase in the perfusion medium and specific perfusate flow characteristics were required to produce the structural changes throughout the brain tissue. When the perfused brain was further dissociated into a cell suspension by mincing and sieving, isolated neurons were obtained, the majority of which retained the proximal parts of their processes. A novel feature of these neurons was the retention of synaptic boutons on the plasma membrane. Presynaptic terminals with mitochondria and vesicles as well as pre- and postsynaptic membranes and densities were observed on the isolated neurons. The neurons were fractionated to 90--95% purity using discontinuous Ficoll density gradient centrifugation with a liquid fluorocarbon as cushion. Highly purified, viable cerebral neurons retaining synaptic complexes are thus available in bulk for neurobiological studies.


Neuritogenic and chemical properties of guinea pig anterior and posterior root myelin. In relapsing experimental allergic encephalomyelitis, recurrent demyelination was found in the anterior roots and dorsal root ganglia with minimal involvement of the posterior roots. To determine whether this is an antigen-related phenomenon, the distribution, type and intensity of the lesions in the proximal PNS of guinea pigs immunized with anterior roots or myelin were compared to those of animals immunized with posterior roots or myelin. Homologous anterior roots were less neuritogenic than posterior roots or posterior root myelin. Thin layer chromatography of myelin samples from anterior and posterior roots, dorsal root ganglia and sciatic nerve revealed the presence of a sulfogalactoglycerolipid, tentatively identified as sulfated galactosylglyceride (SGG) in all but the posterior root myelin samples. Although the PNS lesions of relapsing experimental allergic encephalomyelitis appear to recapitulate the regional distribution of SGG, the reason why its presence in anterior roots myelin renders them less neuritogenic is at present not clear.


Regional distribution of methionine-enkephalin- and beta-endorphin-like immunoreactivity in human brain and pituitary. Concentrations of methionine-enkephalin- (Met-enkephalin) and beta-endorphin-like immunoreactivities were determined in 33 areas of human brain and pituitary using highly sensitive radioimmunoassays in combination with affinity chromatography for the purification of beta-endorphin. It was found that they have quite different distribution patterns, suggesting the existence of both endorphins in independent systems in the central nervous system. Determination of Met-enkephalin and beta-endorphin immunoreactivities in chronic alcoholics and opiate-dependent subjects revealed no gross changes in comparison to the normal subjects.


Regeneration of normal terminal innervation patterns by central noradrenergic neurons after 5,7-dihydroxytryptamine-induced axotomy in the adult rat. The regeneration of central adrenergic axons has been followed between 5 days and 18 months after 5,7-dihydroxytryptamine(5,7-DHT)-induced axotomy in the adult rat, using fluorescence histochemistry in combination with noradrenaline (NA) determinations and [3H]NA uptake measurements. The axonal and terminal degeneration caused by the 5,7-DHT treatment (150 micrograms intraventricularly) was, by 1--2 weeks after injection, accompanied by a 70% reduction of NA in the forebrain and 30% reduction in the brain stem, and by 43--85% reductions in the [3H]NA uptake capacity in various regions of the brain and spinal cord. Signs of sprouting of the drug-lesioned axons were evident along the terminal axon segments at 5 days after treatment. The sprouts increased rapidly in length and number during the subsequent weeks and by 2--6 months after injection new NA terminal systems of relatively normal density and distribution had been re-established in many initially denervated regions. In parallel there was a recovery of endogenous NA and [3H]NA uptake to the pre-injection levels in the brain, and to levels 50--75% of normal in the cervical and thoracic spinal cord. Four successive phases of the regeneration process are distinguished: (1) primary sprouting from the lesioned NA axon stumps, occurring within the first week after treatment; (2) seemingly random growth and proliferation of the newly formed sprouts during the second and third weeks; (3) directed, forward growth of some of the sprouts leading to a partial restoration of the original fibre paths, branching patterns and terminal networks within 3--6 months; (4) a concomitant removal of at least part of the abnormally directed sprouts. Although the original fibre architecture was quite accurately restored in many areas the regeneration was not always correct. Hyperinnervation patterns and abnormal terminal arrangements were often formed, and in the spinal cord the down-growth of the regenerating axons occurred predominantly along a route that is inconspicuous in the normal rat. It is concluded that at least certain types of central neurons regenerate very efficiently provided the conditions are favourable, and that under such conditions axonal regeneration in the mammalian CNS is subjected to regulatory mechanisms that can be very precise. The results provide evidence that the adult mammalian CNS possesses mechanisms for axonal guidance which allow the accurate regeneration of lesioned axonal tracts and branching patterns, as well as mechanisms of recognition making possible the re-establishment of the original terminal connections.


The effects of acute morphine treatment on the incorporation of [3H]L-lysine by normal and regenerating facial nucleus neurons. Although opiates significantly alter RNA and protein synthesis in a variety of neuronal cell types, their effect on the biosynthetic activity of regenerating neurons has not been investigated. In the present study, the effect of morphine on the incorporation of [3H]L-lysine into proteins of facial nucleus neurons was examined by light microscopic radioautography. Silver grains present within various compartments of normal and regenerating (3-, 7-, 14- and 21 days post-axotomy) neurons from saline-treated Wistar rats were compared with the amount present in similar cells from animals receiving 40 mg/kg morphine sulfate i.v. At 14- and 21-days post-axotomy, regenerating neurons were larger and the grain count in the emulsion over these cells was greater than that observed in normal (unoperated) neurons. In normal facial neurons, the accumulation of lysine into the nucleus and nucleolus was significantly lower 60 min after morphine administration. However, morphine's inhibition of lysine incorporation was even more pronounced in regenerating neurons. In these cells, nuclear lysine uptake was depressed at 3 and 7 days, while maximum inhibition of cytoplasmic incorporation occurred at 14-days post-axotomy. Morphine administration decreased nucleolar lysine incorporation at all survival intervals.


Regional variation and absence of large neurons in the cerebellum of the staggerer mouse. Staggerer (sg) is a neurological mutant mouse in which the cerebellar granule cells degenerate after migration to the internal granule cell layer. In addition, the Purkinje cells are abnormal, being ectopic, smaller in size and without tertiary branchlet spines. In this study we report two new observations on this mutant: (1) the effects of the mutation show a regional variation in severity along the mediolateral axis. This variation is seen in the cross-sectional size of the tissue, the extent of cortical folding, as well as the density and cytological appearance of the medium-to-large cortical neurons (MLNs); (2) cell counts were done of 30-day-old mutants and of wild-type controls. The counts revealed that three-quarters of the MLNs of the cerebellar cortex are missing in staggerer. These findings cannot exclude the possibility that Golgi as well as Purkinje cells are absent since the two cannot be distinguished in staggerer. Depending on the number of Golgi cells present, between 60% and 90% of the wild-type number of Purkinje cells is missing in staggerer. The results are discussed in terms of their implications for other studies and for locating the site of staggerer gene action.


Mapping study of brain dopamine- and epinephrine-sensitive sites which cause feeding suppression in the rat. Central injections of dopamine (DA) or epinephrine (EPI) have been found to suppress feeding behavior in hungry rats. In the present study, 24 different brain areas, in 299 animals, were examined to localize the precise region of catecholamine (CA) sensitivity. Essentially all sites outside the hypothalamus, as well as in the medial portion of the hypothalamus, were relatively or totally unresponsive to DA or EPI. The area of greatest sensitivity for both agonists (where they yielded a 50--70% suppression of feeding) was found to be the perifornical region of the lateral hypothalamus, extending from the caudal aspect of the paraventricular nucleus to the caudal aspect of the ventromedial nucleus. Dorsal, lateral, or ventrolateral movement of the injection site away from the fornix and into the zona incerta or the lateral hypothalamic medial forebrain bundle area caused a dramatic reduction in the effectiveness of the CA. These findings are consistent with histochemical studies, which have shown the fornix to be surrounded by CA varicosities, and pharmacological studies, which have shown the perifornical region to be most sensitive to the anorexic effect of centrally injected amphetamine, which releases endogenous CA. It is suggested that the perifornical hypothalamus plays a role in the process of inhibiting food consumption in response to increased dopaminergic and adrenergic activity.


Taurine effects on 45Ca2+ transport in retinal subcellular fractions. The effect of taurine on 45Ca2+ transport by subcellular fractions from the chick retina was examined. An inhibitory action of taurine on 45Ca2+ uptake was observed in retinal fractions incubated for 1--5 min in a Krebs--bicarbonate medium, pH 7.4. In the crude nuclear fraction, 25 mM taurine produced a decrease of 50% in 45Ca2+ uptake; in the crude synaptosomal fraction, taurine reduced 45Ca2+ accumulation by 70%; the maximum inhibitory effect of taurine on 45Ca2+ uptake (80%) was observed in a fraction containing outer segments and pigment epithelium cells. Taurine effect was specific, dose-dependent and related to osmotically sensitive particles. The results suggest a role for taurine in the regulation of calcium fluxes in the retina.


Distribution of hypertrophied locus coeruleus projection to adult cerebellum after neonatal 6-hydroxydopamine. Following treatment as neonates with a high subcutaneous dose of 6-hydroxydopamine (6-OHDA), the projections of the locus coeruleus were mapped in the brains of adult rats. This was done using the technique of unilateral lesions in the nucleus followed by simultaneous determinations of norepinephrine (NE) levels, dopamine-beta-hydroxylase (DBH) activity and synaptosomal [3H]NE uptake in various terminal areas. In particular the cerebellum was subdivided into 3 areas in order to assess any changes from normal in the distribution of the hypertrophied noradrenergic projections here. In vehicle-control rats the lesions resulted in an 80--85% loss of NE in the parietal cortex ipsilateral to the lesion and a 15--20% loss contralaterally. In the control cerebellum the locus coeruleus projection, based upon changes in all 3 markers, is distributed 2/3 ipsilaterally and 1/3 contralaterally with the same pattern present in all 3 subregions. The neonatal 6-OHDA treatment resulted in virtually complete loss of noradrenergic terminals in the cerebral cortex. Following neonatal 6-OHDA treatment cerebellar levels of NE, DBH and [3H]NE uptake increased by between 20--60%, with the smallest increases occurring in [3H]NE uptake. In these rats the locus coeruleus accounted for at least 75--80% of the cerebellar noradrenergic parameters. Unlike control rats however, the lesions in these rats produced only ipsilateral decreases in NE and DBH. On the other hand changes in [3H]NE uptake indicated a normal 2/3 ipsilateral, 1/3 contralateral pattern. It is suggested that two separable events occur in the noradrenergic projection to the cerebellum. The first is the regeneration of an increased number of nerve terminals, or sprouting, and the second is a build-up of synaptic vesicles, or collateral accumulation. The sprouting, judging from the [3H]NE uptake data, occurs with apparently normal distribution, but the accumulation of NE and DBH is confined predominantly to the ipsilaterally projecting axon terminals. This may be the consequence of collateral accumulation resulting from the degeneration of the largely ipsilateral coeruleocortical projection.


Autorhythmicity of spontaneous interictal spike discharge at hippocampal penicillin foci. Penicillin-induced epileptogenic foci in the cat hippocampus show a marked tendency for brief but periodic seizure discharges known as 'interictal spikes' (IS). Here, each IS is shown to be followed by a marked elevation and subsequent slow fall-off of the focal seizure threshold. The time constant of this process approximates the spontaneous inter-IS interval and these two parameters appear to vary in concert. The timing of the IS train is always reset by interjected ISs but not by stimuli that are subthreshold for the IS. In sum, this modulation of focal excitability does not appear to be imposed by local or projected rhythmic activity other than that initiated by the IS itself. The firing patterns of the majority of observed hippocampal single units in the vicinity of the focus show a prolonged suppression of spontaneous firing for from 2 to 10 sec or more after each IS, independent of whether the IS was spontaneous or elicited. A smaller number of units show delayed, intense activation following each IS. Both of these forms of response appear to originate from large cells in and near the pyramidal cell body layer. Assuming that these single unit data represent a sampling of pyramidal cell discharge, then the prevalence of a prolonged post-IS pause suggests that the rhythmicity of spontaneous penicillin foci derives from an inhibitory phasing of the population based paroxysmal activity. The periodic spontaneous IS discharge can be viewed, therefore, as a locally regulated, autorhythmic process impressed upon the activity of the neuronal population by the development of a functional suppression of unit activity following each IS.


Effects of thyroxine on postnatal cell acquisition in the rat brain. The effects of treatment with L-thyroxine (3 micrograms by subcutaneous injection daily from birth) on cell acquisition in the rat brain were studied during the first 3 postnatal weeks. In the forebrain, thyroxine has no effect on cell proliferation in the first 6 days, but it causes decreased cell acquisition from 12 to 21 days so that cell number becomes significantly reduced. Estimates of cell proliferation kinetics and of cell death in the lateral ventricular subependymal layer show no apparent abnormality. In the cerebellum, treatment from birth leads to increased cell proliferation during the first week: in comparison with controls, the rate of [3H]thymidine incorporation into DNA, thymidine kinase activity, and the number of cells both in the major germinal site (external granular layer: EGL) and in the whole cerebellum are elevated. This initial effect of thyroxine appears by day 3 and is short-lived, being no longer evident after day 6. The build-up of cell numbers in the EGL at day 6 seems to be related to a preceding, transient retardation of cell migration from this layer rather than to an acceleration of cell replication, since cell cycle parameters are normal. From day 12 the rate of [3H]thymidine incorporation into DNA is severely reduced in treated rats. Advancement of cellular differentiation rather than increased cell death in the EGL appears to be involved in this phenomenon.


Facilitation of memory consolidation by vasopressin: mediation by terminals of the dorsal noradrenergic bundle? Administration of arginine-vasopressin (AVP, 5 micrograms, s.c.) immediately after the learning trial results in a long-term facilitation of a one-trial learning passive avoidance response. This effect of AVP is absent in animals with prior destruction of the ascending dorsal noradrenergic bundle by bilateral microinjection of 6-hydroxydopamine (6-OHDA). Postlearning local microinjection of a minute amount of AVP via chronically implanted cannulae into the locus coeruleus did not influence passive avoidance behavior. Upon injection into the midbrain dorsal raphe nucleus, however AVP facilitated passive avoidance behavior. This effect, however, was absent in rats receiving previous microinjection of 5,6-dihydroxytryptamine (5,6-DHT) or of 6-OHDA into the dorsal raphe nucleus. Bilateral 6-OHDA-induced lesions of the nucleus accumbens or 5,6-DHT-induced destruction of the dorsal raphe nucleus did not prevent the effect of AVP administered subcutaneously. The data suggest that vasopressin facilitates memory consolidation processes by modulating noradrenergic neurotransmission in terminals of the dorsal noradrenergic bundle. The serotoninergic neuronal network originating from the dorsal raphe nucleus has a secondary--norepinephrine-mediated--influence upon these processes.


Biochemical mapping of the noradrenergic ventral bundle projection sites: evidence for a noradrenergic--dopaminergic interaction. Norepinephrine (NE) and dopamine (DA) concentration and dopamine turnover were measured 12 days after a unilateral or bilateral noradrenergic ventral bundle (VB) transection to determine the noradrenergic projection sites and possible interactions with dopaminergic systems. Both bilateral and unilateral VB transection resulted in a significant reduction of NE of the nucleus accumbens, lateral septal nucleus, medial forebrain bundle, ventromedial nucleus, dorsomedial nucleus and medial amygdaloid nucleus. Bilateral transection also decreased NE content of the median eminence and the periventricular and arcuate nuclei. In the medial preoptic nucleus, the nucleus interstitialis striae terminalis and the central gray catecholamine area, bilateral transection significantly decreased NE concentrations while unilateral lesions had no significant effect. The anterior hypothalamic, lateral preoptic, and paraventricular nuclei responded to bilateral VB transection with a decrease in NE concentration and to unilateral lesion with a bilateral increase in NE. In the dorsal hippocampus and the caudate nucleus, bilateral lesions had no effect on NE concentrations while unilateral transection significantly decreased NE concentrations. Regions in which neither bilateral nor unilateral VB transection produced a significant change in NE content are the olfactory tubercle, the nucleus tractus diagonalis, substantia nigra pars compacta and reticulata, ventral tegmental area, habenula, superior colliculus, and the cingulate and piriform cortices. Transection of the noradrenergic ventral bundle also produced changes in dopaminergic systems suggesting a noradrenergic--dopaminergic interaction. Bilateral VB transection decreased the dopamine concentration and turnover in the nucleus accumbens, increased steady-state levels and turnover in the nucleus tractus diagonalis and increased dopamine concentration in the lateral septum. Unilateral VB transection decreased DA concentration bilaterally in the caudate nucleus, olfactory tubercle, nucleus accumbens and the nucleus interstitialis striae terminalis but increased concentrations in the substantia nigra pars reticulata (ipsilateral) and in the ventral tegmental area (bilateral). These results indicate a broad projection field for the noradrenergic ventral bundle and suggest a noradrenergic--dopaminergic interaction.


Peripheral input pathways projecting to the motor cortex in the cat. The possibility that the motor cortex receives peripheral input directly from the thalamus was examined using the evoked potential method and the following results were obtained. Potentials in the motor cortex evoked by stimulation of superficial radial (SR) or group II deep radial (DR) nerve were neither abolished nor delayed by ablation of the sensory cortex. Potentials in the motor cortex evoked by stimulation of group II DR nerve were most severely reduced by interruption of the spinocervcial tract. Potentials evoked by stimulation of SR nerve were more severely reduced in the sensory cortex than in the motor cortex by section of the dorsal funiculus or cooling of the cuneate nucleus. The size of evoked potentials in the motor cortex increased rapidly when stimulus intensity to DR nerve exceeded the threshold to group II fibers. The results suggest that some inputs from the SR and group II DR nerves reach the motor cortex without a relay through the sensory cortex.


Thalamic projections to the feline motor cortex studied with horseradish peroxidase. Cells in the thalamus projecting to the distal forelimb regions of the motor cortex, area 3a, and the sensory cortex were identified with horseradish peroxidase (HRP). These cortical areas were defined by mapping evoked potentials from superficial and deep radial nerve stimulation. Following injections into the motor cortex, the labelled cells were distributed throughout a large region (greater than 2 mm wide) in the ventral portion of the ventral lateral nucleus (VL). The border area between VL and the ventral posterolateral nucleus (VPL) also contained labelled cells. The region containing labelled cells following injections into area 3a was in the rostral, dorsal VPL, and overlapped with the region containing cells labelled by injections into the motor cortex. Cells labelled by injections into the sensory cortex were near the center of VPL distinctly separated from those labelled after injections into either area 3a or the motor cortex.


Receptive fields of thalamic neurons projecting to the motor cortex in the cat. The locations and receptive fields of thalamic neurons projecting to the motor cortex were examined and the following results were obtained. (1) Neurons located at the border area between nucleus ventralis lateralis (VL) and nucleus ventralis posterolateralis (VPL) could be activated antidromically from the motor cortex. (2) These neurons received topographically organized somesthetic inputs arising from skin and deep receptors. (3) The receptive fields of neurons in the small area of the motor cortex where these thalamic neurons projected could be examined in 8 instances. In 6 instances, the cortical neurons and the thalamic projection neurons were activated by exactly the same stimuli in the periphery. (4) Removal of the sensory cortex did not significantly change the characteristics of afferent inputs from the periphery to the motor cortex. (5) It is concluded that the motor cortex receives somesthetic inputs directly from the thalamus. The functional role of these inputs was discussed in relation to the known cortical reflexes.


Role of the paleostriatum in species-typical display behavior of the lizard (Anolis carolinensis). In a comparative study of forebrain mechanisms of species-typical behavior, unilateral lesions were placed in the subpallial telencephalon of male green anolis lizards (Anolis carolinsis), in which there is an almost complete decussation of the optic nerve. Responses to a conspecific male antagonist in a territorial confrontation were then tested when the subject's vision was limited to an eye leading to either the normal or lesioned hemisphere. In lizards with lesions involving the paleostriatum and lateral forebrain bundle, there was an elimination of or marked deficit in the performance of the challenge display while signature displays and measures of general activity were not significantly affected. Lesions predominantly in anterior or posterior dorsal ventricular ridge resulted in no significant deficit in any behavioral measure.


Inhibition of spinal cord interneurons by narcotic microinjection and focal electrical stimulation in the periaqueductal central gray matter. Single cell evoked activity was recorded from spinal cord interneurons in rats prepared with microinjection cannulae or stimulating electrodes in the periaqueductal central gray matter (PAG). Morphine microinjections (4-16 microgram) inhibited the response evoked by a noxious stimulus in 55% of the wide dynamic range neurons tested. Microinjections of etorphine (0.25-0.5 microgram) inhibited 82% of the nociceptive neurons tested. Neither drug inhibited neurons which responded only to innocuous mechanical stimulation. The inhibition of wide dynamic range neurons produced by narcotic microinjection was antagonized by naloxone (1 mg/kg, i.p.) in 7 of 11 cases. Control experiments indicated that the effects obtained with microinjections could not be attributed to the drugs' diffusion to the spinal cord. Focal electrical stimulation of the PAG inhibited the responses to noxious stimuli of 60% of wide dynamic range neurons but was without effect on the responses of neurons that were activated only by innocuous stimuli. These experiments directly demonstrate that narcotic analgesics restricted to an intracerebral site of action activate a neural system which preferentially inhibits the responses of spinal cord wide dynamic range neurons to noxious stimuli. The system has a specificity for nociceptive input since non-nociceptive neurons were unaffected. Directly comparable results were produced by electrical stimulation of the PAG, supporting the concept that stimulation and narcotics modulate the transmission of nociceptive information by similar mechanisms.


Sodium dependence of the nerve growth factor--regulated hexose uptake in chick embryo ganglionic cells. Embryonic dorsal root ganglionic cells, when incubated in vitro in the absence of nerve growth factor (NGF) undergo a general metabolic degeneration which is preceded by certain changes in permeation properties. Previous studies demonstrated that NGF can rapidly modulate permeation properties which regulate the availability to the cell of an important energy source, glucose. Hexose uptake was determined by measuring the ability of the cells to accumulate [3H]labeled 2-deoxy-D-glucose. The work reported here shows that the NGF-dependent portion (about one-third) of the total specific hexose uptake was also dependent on the presence of Na+, with the apparent uptake constant (Kt) for deoxyglucose varying inversely with an external Na+ concentration of 70-140 mM; Vmax was unaffected in this range. Preincubation of ganglionic cells with 10 mM ouabain for 15-60 min, followed by a pulse with [3H]-deoxyglucose, also resulted in 50-95% reduction of the NGF-sensitive uptake. A similar pretreatment of cells with veratridine gave a 25-50% reduction in uptake. The NGF-controlled hexose uptake was also energy dependent, being diminished 50-95% after a 30-90 min preincubation with 2 mM 2,4-dinitrophenol. Uptake activities for other substrates (alpha-aminoisobutyric acid, uridine) which exhibited NGF regulation were likewise Na+-sensitive. These results indicate that availability of major energy substrates to NGF-dependent dorsal root ganglionic neurons is controlled by sodium gradients across their membranes. It is conceivable that NGF provides for maintenance and development of its target neurons by acting on such sodium gradients and, consequently, regulating the intake of essential nutrients.


Modification of a Kowa RC-2 fundus camera for self-photography without the use of mydriatics. Research on retinal circulation during space flight required the development of a simple technique to provide self monitoring of blood vessel changes in the fundus without the use of mydriatics. A Kowa RC-2 fundus camera was modified for self-photography by the use of a bite plate for positioning and cross hairs for focusing the subject's retina relative to the film plane. Dilation of the pupils without the use of mydriatics was accomplished by dark adaption of the subject. Pictures were obtained without pupil constriction by the use of a high speed strobe light. This method also has applications for clinical medicine.


Amplitude and fall-time discrimination of unit spike activity using TTL. An inexpensive and reliable window discriminator simply constructed using TTL integrated circuits is described. The device will discriminate between unit spikes on the basis of amplitude alone or amplitude and fall-time, and simultaneous analysis of two separate spikes is possible. All pulse outputs and amplitude and fall-time windows may be displayed allowing the setting up of window criteria to proceed under direct visual control.


Penile reflexes and copulatory behavior in male rats following lesions in the bed nucleus of the stria terminalis. Male rats with large lesions in the bed nucleus of the stria terminalis (BNST) had more intromissions preceding ejaculation (if they ejaculated at all), longer intervals between intromissions, and longer postejaculatory refractory periods than control animals. In tests for penile reflexes, BNST males were similar to control males in every respect. The copulatory deficits in BNST males are probably not mediated by a change in penile reflex potential.


Electrically quiet temperature controller. A circuit for an electrically quiet temperature controller is described that is suitable for controlling the temperature of a neurophysiological preparation above ambient temperature. By not generating spurious electrical signals it facilitates the recording of low level biological potential changes when temperature control is required. The device, constructed of standard electronic components, uses a thermistor as a sensing element and an ordinary heat lamp or heating strip as a heating element.


A note on the distribution of glial cells in the molecular layer of the dentate gyrus. The distribution of the perikarya of astrocytes and other glial cells in the molecular layer of the dentate gyrus has been studied in gold chloride-sublimate preparations of rats and of normal and reeler mice, and in plastic embedded material from young adult rats. Contrary to previous reports (Rose et al. [7]), we have found no evidence for a distinct "line" or "band" of astrocyte cell bodies along the interface between the zones of termination of the entorhinal and hippocampal afferents to the dentate gyrus. Indeed, apart from a conspicuous accumulation of astrocytes immediately beneath the pial surface and hippocampal fissure, the distribution of glial cells across the extent of the molecular layer appears to be more or less random. In view of this it is difficult to ascribe a critical role to the astrocytes in either determining the normal distribution of afferent fibers to the dentate gyrus or in promoting their re-organization following its partial deafferentation.


Further characterization of fat diet-induced changes in responsiveness to estrogen and glucose. Possible reasons for hyperresponsiveness to the anorexic influence of estrogen of rats fed a high-fat (F) diet were explored. It was found that (1) hyperresponsiveness appeared unrelated to body weight, (2) other estrogenic effects (upon vaginal epithelia and upon mating behavior) were normal in F-fed rats, (3) hyperresponsiveness to estrogen was not a result of alterations in brain dopamine or norepinephrine, (4) F-fed rats were also hyperresponsive to postabsorptive satiating effects of intragastric glucose loads. Thus, an altered glucose metabolism of F-fed rats may be related to an increased responsiveness to the anorexic effects of estrogen.


The effects of stimulation of trigeminal sensory afferents upon caudate units in cats. This investigation assessed the influences of trigeminal primary sensory afferents upon caudate neuronal activity in locally anesthetized and chloralose anesthetized cats. Afferents from jaw elevator stretch receptors were stimulated via electrodes in the trigeminal mesencephalic nucleus (Mes 5). Afferents from dental and periodontal receptors were stimulated via electrodes in the inferior dental nerve (IDN). Low intensity electrical stimulation of either locus evoked caudate neuronal responses with Mes 5 being more effective. Higher intensity stimulation of IDN in chloralose anesthetized cats was used to determine if thresholds of trigeminal evoked caudate responses corresponded to thresholds of particular fiber groups in the sensory afferent. In all tested units, neuronal responses were only evoked when stimulation was suprathreshold for both A beta and A delta fibers. These data were discussed in relation to processing of oropharyngeal sensory information within the basal ganglia. Possible implications for bucco-lingual dyskinesias were noted.


Influence of thalamic cooling on sensory responses in association cortex. Evoked responses to light flash, click, and paw stimuli were recorded in the four cortical association areas in the acutely prepared cat. Average evoked responses (AEP) for 100 trials were formed before, during, and after localized cooling in the midline thalamus. Cooling of the midline thalamus reduced the magnitude of responses to click and paw stimuli, and increased or did not change the responses to light flash. There was very little similarity in trial-to-trial fluctuations of EP magnitude across cortical areas, and cooling did not reduce the similarity that existed. Waveform similarity was reduced by cooling for responses across the cortex to a single stimulus modality, whereas similarity of responses in a single cortical area to all three stimuli was not changed. The temporal components of the AEP influenced by thalamic cooling were different for different stimuli and cortical locations. It was concluded that the midline thalamo-cortical projection through the centromedian area to association cortices is particularly well-differentiated for multisensory responses in a single cortical region, and that the system should not be thought of as nonspecific but as convergent or multisensory.


Plasma and cerebrospinal fluid alpha-MSH levels in the rat after hypophysectomy and stimulation of pituitary alpha-MSH secretion. Immunoreactive alpha-MSH was measured in cerebrospinal fluid (CSF) and plasma of rats. While treatment with haloperidol increased alpha-MSH levels in the plasma concentration of alpha-MSH in the CSF showed little change. Hypophysectomy also had little effect on the concentration of alpha-MSH in the CSF despite the fall in plasma alpha-MSH levels. This lack of correlation between alpha-MSH levels in the CSF and plasma suggests that the systemic circulation does not deliver alpha-MSH to the CSF. The apparently normal levels of alpha-MSH in the hypothalamus after hypophysectomy suggests that this tissue is able to synthesize alpha-MSH and it is possible that the hypothalamus is a source of the alpha-MSH in the CSF.


Inhibitory pathway from the frontal cortex to the hypothalamic ventromedial nucleus in the rat. Stimulation of the dorsal frontal cortex (area 10, FCtx) evoked two negative waves with short latencies (N1 and N2) followed by a large, longlasting positive wave (P) in the ventromedial nucleus (VMH) as well as in the more dorsal structures in the hypothalamus and the ventral thalamus. Since the N1 followed high frequency stimulation, it was concluded to be due to antidromic activity. Double or triple pulse stimulation summated the P, and reduced the amplitude of the negative waves of the second and the third responses. VMH neuronal discharges were also decreased during the time course of the P. Therefore, the P was concluded to be composed of the IPSPs. VMH neuronal discharges were frequently superimposed on the N2, indicating the origin of this wave to be EPSPs. Strychnine reduced or blocked the inhibition of the VMH neurons caused by not only FCtx stimulation but also glycine application. The results indicate that the VMH receives both excitatory and inhibitory projections from the FCtx, and the inhibition may be transmitted by glycine.


The effects of folate deficiency and oestradiol administration on the plasma free amino acid concentrations of the immature hen. 1. Free amino acid concentrations were measured in the blood plasma of immature pullets receiving a folate-deficient diet and injected with folate and/or oestradiol, with appropriate controls. 2. Folate deficiency caused a decrease and oestradiol administration an increase in the plasma concentration of most of the amino acids studied. 3. Plasma glycine concentration increased in foliate deficiency and decreased with oestradiol treatment. 4. All the observed effects could not be readily explained in terms of the known metabolic role of folate in amino acid metabolism. 5. The results did not indicate that the role of folate in amino acid metabolism was significant in the inhibition of oestradiol-stimulated oviduct growth.


Hypothalamic unit responses to alimentary perfusions in the anesthetised rat. Single unit discharges in the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LH) were extracellularly recorded in urethane anesthetised female rats, while various solutions were perfused through the stomach or duodenum via implanted polythene tubes. Perfusates, which were maintained at 38 degrees C, were 0.9% (w/v) NaCl, 2.5% NaCl, 5.25% glucose, 30% glucose, 5.0% casein hydrolysate, and liquid food. Only units which did not respond to somatosensory stimuli were tested. One hundred and twenty six units were recorded for periods of up to 3 hr, occasionally longer, in 57 animals. Of these, 74 were recorded during gastric perfusions and 52 during duodenal perfusions. Distension of the stomach elicited changes in firing rate in 16 LH and 8 VMH units. Both increases and decreases in firing rate in response to gastric distension were observed in both the LH and VMH. There was no evidence that nutrient or osmotic properties of the perfusates exerted any modifying influence on hypothalamic unit discharges. Distention of the duodenum by the perfusions elicited changes in firing rate in 12 LH and 6 VMH units. In this case all LH units decreased firing and all VMH units increased firing during distension of the lumen. In addition 2 VMH units appeared to increase their firing rate in association with glucose perfusions. The results are discussed in terms of the role of gastrointestinal feedback to the hypothalamus in food intake regulation.


Role of limbic system in the control of hamster growth. Rostral septal lesions accelerate somatic growth in adult hamsters. This study tested the hypothesis that this effect results from damage to fibers of passage by observing the effects of transections of septohippocampal and septohypothalamic connections on growth. We attempted to identify these fibers further by (a) measuring spectrofluorometrically changes in the monoamine concentrations in hippocampus, cerebral cortex, corpus striatum, and diencephalon, (b) staining the degenerating axons after septal lesions and the two cuts, and (c) examining the correspondence between such damage and the acceleration of growth. Both knife cuts accelerated somatic growth and were associated (as well as septal lesions) with significant depletions of serotonin (-27 to -57%) and norepinephrine (-27 to -60%) in the hippocampus, with less consistent depletions of these monoamines in the cerebral cortex, and with no changes in regional dopamine content. All three procedures were associated with degeneration in the hippocampal formation and its fiber systems. Thus, fibers interconnecting hippocampus and brainstem, and passing through septum, exert tonic suppression over somatic growth in adult hamsters.


The localisation of beta-N-acetyl-glucosaminidase in the oviduct of the domestic fowl. 1. Beta-N-acetylglucosaminidase [EC 3.2.1.30] activity in the oviduct of the domestic fowl has been studied using biochemical and histochemical methods. 2. The principal source of the enzyme was the isthmus, where the enzyme was localised within the less dense region of the dual density granules which characterise this portion of the oviduct.


Apparatus for EEG recording and electrical stimulation of discrete brain areas in an unrestrained small animal. An apparatus that permits the observation of behavior, recording of EEG and electrical stimulation of the brain can be built from readily available and inexpensive components. This type of apparatus has a variety of uses in biomedical research.


Variations in plasma prolactin, thyroid hormones, gonadal steroids and growth hormone in turkeys during the induction of egg laying and moult by different photoperiods. 1. Concentrations of prolactin, growth hormone, testosterone, progesterone, thyroxine and triiodothyronine were measured in the blood plasma of female turkeys during successive periods of egg laying, a decline in lay, a moult induced by a short photoperiod (6 light: 18 dark) and a resumption of egg laying induced by a long photoperiod (16L:8D). 2. Concentrations of prolactin, growth hormone, testosterone and progesterone were higher in laying birds than in birds which were moulting or not laying. 3. The concentration of testosterone, but not of the other hormones studied, increased significantly during the period of profuse moult. 4. Concentrations of the thyroid hormones did not change with the varying physiological condition of the birds. However, the concentration of thyroxine was depressed by the long photoperiod.


An improved simple tungsten microelectrode. An improvement to tungsten-in-glass microelectrode has been made which requires to special skills. It involves the introduction of a gel solution into the glass micropipette which surrounds and binds the tungsten wire along its full length. A significant damping of microphonic effects is produced and a good fit between tungsten and glass near their tips becomes less critical for success. The electrode was found to be very stable over long recording sessions.


A study of the growth of the alimentary tract of the young cockerel. 1. The growth of the alimentary tract of male domestic fowl has been described from measurements of the dry weight of the whole and component parts of the tract from hatching to 10 weeks of age. 2. Quadratic regression equations were derived to express the growth of the birds and the growth of their alimentary tracts. 3. From hatching to 2 weeks there were marked alterations in the proportions which the different parts represented of the size of the whole tract.


Variations in plasma growth hormone concentrations in laying hens. 1. Variations in plasma concentrations of growth hormone (GH) and luteinising hormone (LH) were measured by radioimmunoassay in blood samples taken during the ovulatory cycle of the domestic hen. 2. A peak in LH concentrationas observed 4 h prior to ovulation. 3. Plasma GH concentrations were quite variable but a significant increase was observed between 2 h before and 2 h after ovulation and the concentration remained elevated for about 4 h thereafter.


Sodium consumption following lesions surrounding the anteroventral third ventricle. Consumption of sodium solution was measured in rats with lesions of the anteroventral third ventricle (AV3V) and maintained on sodium deficient chow. Rats with AV3V lesions consumed less sodium than control animals, and increased their sodium consumption following a subcutaneous injection of Formalin. These data indicate that the AV3V ablation alters the nature of the regulatory control of sodium but does not render animals insensitive to plasma sodium levels.


A technique for the controlled fracture of micropipette electrode tips. A method is described for the controlled fracture of electrolyte-filled micropipette electrodes, so that their tip diameter and DC resistance becomes suitable for extracellular recording from individual neurones. The technique is simple and has a low wastage rate. The apparatus used is that employed in conventional microelectrode recording.


Effect of diurnal or nocturnal heat stress on egg formation. 1. Mature laying hens were subjected to ambient temperatures sufficient to maintain body temperature of 43 degrees C for periods of 6 to 7 h during the day (eight periods) or the night (five periods). This did not reduce total daily food consumption. 2. The effect of heat stress during the day was mostly on egg-shell quality, being adverse and significant. During the night heat stress caused a significant decrease in egg production, its effect during the day was less marked in this respect. 3. Heat stress thus seems mostly to affect the early stages of shell formation, while its effect on egg production seems to depend on the time at which it occurs in relation to ovulation. 4. These results suggest that egg production is directly affected by heat stress; prolonged heat stress probably also acts indirectly, by suppression of food intake.


Energy and nitrogen metabolism of chickens infected with either Eimeria acervulina or Eimeria tenella. 1. The effects of sublethal infections of E. acervulina and E. tenella on the energy and nitrogen metabolism of groups of five broilers aged 16 d were studied for 16 d in respiration chambers. 2. The metabolisable energy content of the diet for chickens infected with E. acervulina was 0.689 of its gross energy content and N retention was 42.5 g/100 g N intake compared with 0.738 and 47.1 g respectively, in uninfected pair-fed controls. Chickens infected with E. tenella were similarly affected. 3. Efficiency of utilisation of ME by chickens infected with E. acervulina was 0.43 during the first 8 d after infection, and 0.52 during the second 8 d compared with an overall efficiency by non-infected chickens fed ad libitum of 0.73. Maintenance energy requirement of infected chickens was higher during the first 8 d after infection than during the second 8-d period. 4. Body composition measurements showed that of the total gain in weight of chickens infected with E. acervulina, only 7.5 g/kg gain was fat and 213 g/kg was protein compared with 45 g and 210 g respectively for non infected chickens fed ad libitum. 5. E. acervulina and E. tenella infections reduced the apparent digestibility of total mineral, calcium and phosphorus.


Energy and nitrogen metabolism of chickens subjected to infection and reinfection with Eimeria acervulina. 1. The effects of E. acervulina on energy and nitrogen metabolism were studied in respiration chambers on four groups of four broilers aged 16 d: group C was infected with 1.1 x 10(6) oocysts/bird on day 1 and fed ad libitum, while groups A, B and D were pair-fed to group C to day 16 of the experiment. On day 17, groups A and C were given 5.0 x 10(6) oocysts/bird and fed ad libitum, while group B was pair-fed to group A and group D was pair-fed to group C to the end of experiment on day 32. 2. Dietary ME as a proportion of gross energy (0.68) and N retention (42 g/100 g N intake) were reduced in the infected group C compared with pair-fed controls (0.75 and 49 g, respectively) for the period 1 to 16 d. Subsequent challenge of group C saw no effects on the two variables, but metabolisability (0.65) and N retention (33 g) were significantly reduced in group A when infected for the first time on day 17. 3. The daily heat production and food intake of group A infected for the first time with E. acervulina on day 17, and group B, their pair-fed controls, were reduced during days 20 to 25 but no such reductions were observed in group C, receiving a challenge dose of E. acervulina, and group D, non-infected pair-fed to group C. The efficiency of utilisation of ME for growth of groups C and D was 0.60 over the 17 to 32 d period. 4. Challenge of immune birds did not affect the apparent digestibility of total minerals, calcium and phosphorus.


Phanton limb sensation under subarachnoid and epidural analgesia - a comparative clinical study of two hundred cases. Two hundred patients scheduled for various surgical procedures, under subarachnoid and epidural anaesthesia were divided in two groups of 100 for each technique. Subarachnoid analgesia was obtained with five per cent lidocaine, while epidural analgesia was accomplished with 1.5 per cent or 2 per cent lidocaine with adrenaline. This study shows that phantom sensation is painless and self limiting and that it lasts only for the duration of motor and proprioceptive blockade. It does not require any special treatment except psychotherapy, supplemented if needed by tranquilizers. Patients should be positioned after motor blockade has been established.


In vivo neutron activation analysis for bone calcium (INVAA) in malignant hyperthermia susceptible patients. Some non-rigid Malignant Hyperthermia Susceptible (MHS) patients have a greater than normal incidence of fractures. Radiologically their long bones are slightly thinner than normal. Excessive numbers of caries because of thin dental enamel may also be present. The Malignant Hyperthermic (MH) defects thus appears to involve cells of bone appendages as well as of muscle. We have measured the concentration of calcium in bone by neutron activation analysis and have found it to be reduced in both non-rigid and rigid malignant hyperthermia susceptible patients. The reductions were particularly marked for the non-rigid patients. Bone calcium concentrations were lower in males than in females and in those under 16 and over 60 years of age. This is additional evidence is favour of the hypothesis that malignant hyperthermia is a widespread defect affecting tissues and organs throughout the body.


Comparison of droperidol, haloperidol and prochlorperazine as postoperative anti-emetics. The results of this study demonstrate that prochlorperazine, haloperidol and droperidol are all effective post-operative anti-emetic compounds when compared to saline but vary in onset of activity and duration of action. Haloperidol has the shortest onset of action, being effective within 30 minutes of intravenous administration. Prochlorperazine has an intermediate onset of action and droperidol is the slowest of the three compounds but the only one to provide significant anti-emesis 4-24 hours following administration. Our data suggest that a combination of haloperidol and droperidol may be more effective as an anti-emetic than any one of the compounds used alone.


Introduction of central venous pressure catheters through arm veins with a high success rate. Studies were carried out to develop a more successful method of inserting central venous catheters through arm veins without using electrocardiographic or fluoroscopic monitoring. It was found that a running infusion attached to a Sorensen catheter gave a success rate of 48 per cent. The highest success rates (98 per cent) occurred when the basilic vein was used, with the patient positioned so that the upper part of the body was raised at 45-90 degrees to the horizontal and using a Bardic 16 gauge catheter with a special insertion technique, which is described. This represents a great improvement over the usual success rate of 70 to 80 per cent.


Prophylactic blood patch does not prevent post lumbar puncture headache. Of 86 patients in whom accidental puncture of the dura occurred during insertion of a needle for induction of epidural analgeisa for labour and delivery, 11 received a prophylactic blood patch at the completion of delivery. Of the 75 patients with no prophylactic blood patch, 59 per cent developed post-lumbar-puncture headache, while 54 per cent of those who had a prophylactic blood patch developed headache. The prophylactic blood patch appears to have no value in preventing post-lumbar-puncture headache in this small group of patients.


Anaesthesia for tracheal resection. Modified use of the Carden Tube. Surgical procedures involving sharing of the airway between the anaesthetist and surgeon, such as bronchoscopy, microlaryngeal surgery and tracheal resection impose special problems on the anaesthetist. The surgeon requires unrestricted surgical access, whereas the anaesthetist must ensure adequate and safe pulmonary ventilation and anaesthesia. This case report describes a two stage technique for management of the airway and ventilation during tracheal resection for stenosis. Initially a modified Carden tube with a ventilating injector was used through a tracheostomy stoma and subsequently an orotracheal tube was substituted. Anaesthesia was maintained entirely by the inravenous route. The surgical access was unrestricted and there was no pulmonary contamination.


Acute airway obstruction: a complication of aluminum tape wrapping of tracheal tubes in laser surgery. A case is reported of acute airway obstruction arising from the use of a tracheal tube wrapped with aluminum tape during laryngeal surgery with a carbon dioxide laser. Problems associated with aluminum tape wrapping of tracheal tubes are discussed.


Laryngocele--an anaesthetic hazard.

Laryngocele--an anaesthetic hazard. The authors report a case in which a previously unrecognized laryngocele in an eight-year-old child was accidentally intubated and inflated after induction of anaesthesia for tonsillectomy. The nature and diagnosis of laryngocele are discussed.


Knotting of an epidural catheter: a case report. Difficulty with removal of an epidural catheter is described due to formation of a knot near the end of the catheter. It is stressed that in the lumbar area an epidural catheter should never be inserted more than 5 cm into the epidural space, as curling with knot formation may occur. Removal may be attempted by pulling on the catheter if testing of a similar catheter indicates that it will withstand the tension. The patient and the spouse should be kept informed and involved in the decision-making for medico-legal reasons.


Relation of precurarization to suxamethonium to provide ease of intubation and to prevent post-suxamethonium muscle pains. Tubocurarine 0.05 and 0.07 mg.kg-1, gallamine 0.1 and 0.2 mg.kg-1 and pancuronium 0.01 and 0.02 mg.kg-1 given three minutes before suxamethonium 1.0, 1.5 and 2 mg.kg-1 in groups of 10 patients each (total 210 patients) to compare ease of tracheal intubation and incidence of post-suxamethonium muscle pain. These were compared with a control group of suxamethonium 1.0, 1.5 and 2 mg.kg-1 given alone after thiopentone 5 mg.kg-1. On analysis, tubocurarine 0.07 mg.kg-1 and suxamethonium 2 mg.kg-1 was the ideal combination with the best intubation conditions and the lowest incidence of post-suxamethonium muscle pains. The second best combination was gallamine 0.2 mg.kg-1 and suxamethonium 2 mg.kg-1. Pancuronium 0.01 mg.kg-1 and 0.02 mg.kg-1 in combination with suxamethonium 2 mg.kg-1 were satisfactory, although less efficient than the combination with either tubocurarine or gallamine.


Abnormal enzyme phenotype (E1a E1f): normal response to succinylcholine. The enzyme serum cholinesterase responsible for the hydrolysis of the muscle relaxant succinylcholine exists in the form of several variants. These may be identified in serum by using substances which inhibit their activity to different degrees. The heterozygote for the atypical and fluoride resistant enzymes (E1a E1f) is one of the phenotypes which has been reported to be sinsitive to succinylcholine. A case is described where succinylcholine given on two separate occasions did not induce apnoea in an individual phenotyped as E1a E1f by at least five methods of inhibition. This is the first reported example of such insensitivity to the drug in this phenotype. Temperature activities for the patient's serum over the range of 20 degrees C to 45 degrees C differed from that of an established E1a E1f phenotype used as a control. There was a progressive inactivation of the control serum at temperatures higher than 35 degrees C, as previously reported for this phenotype. Activity in the serum of the subject of this study did not exhibit the peak activity at 35 degrees C but continued to rise and probably reached a peak between 40 degrees C and 45 degrees C. The significance of these results in the context of current methods of phenotyping is discussed.


Inline blood gas analysis by gas chromatography in patients during and after coronary artery surgery. A system was evaluated of measuring Pao2 and Pao2 by an inline sensor in the brachial artery and gas chromatography. Eight patients having coronary artery vein grafts were studied during anaesthesia, operation, perfusion and for 24 hours afterward. Compared to conventional blood gas analysis by polarography (electrodes), the chromatographic method gave readings for Pao2 which were not significantly different during normothermia. During hypothermic perfusion, the chromatographic system read significantly higher than the bench electrode, due at least in part to a difference in temperature correction. For Pao2 the correlation between the two methods was close and differences were clinically insignificant. The Sentorr blood-gas analyser provides a sensitive, accurate indicator of changes in oxygenation, ventilation and circulation during anaesthesia and in the intensive care unit.


Halothane solubility in blood during cardiopulmonary bypass: the effect of haemodilution and hypothermia. The influence of haemodilution and cooling on the solubility of halothane in blood during cardiopulmonary bypass was studied in six normothermic and six hypothermic patients undergoing open-heart operations. The solubility of halothane in blood was 2.17 at 30 degrees C and 1.34 at 37 degrees C. There was also an increase in the blood/gas partition coefficient of about 8.7 per cent for each degree celsius of temperature fall. These changes in haemodiluted blood explain the different anaesthetic requirements observed in patients undergoing cardiopulmonary bypass, either at normal temperature or at moderate hypothermia.


Intubation and other experiences in cardiac surgery: the consumer's views. Recently publications have advocated earlier weaning and early extubation of the trachea in patients after cardiac surgery. Greater comfort of the patients is one of the advantages claimed for this policy. One hundred consecutive adult patients were questioned on the fifth postoperative day to assess the relative comfort or discomfort of the patients during tracheal intubation and ventilation. Overnight tracheal intubation and ventilation were easily tolerated by over 90 per cent of patients who had received morphine and diazepam. There was a high incidence of amnesia. Some of the other claimed advantages appear inconclusive and further study is desirable to elucidate the effect of early removal of the tracheal tube upon the indicence of pulmonary complications.


Cardiac effects of magnesium with special reference to anaesthesia: a review. The role of magnesium in myocardial metabolism and the effects of magnesium deficiency on myocardial contraction and the electrocardiogram have been described. The causes of a magnesium deficiency have been discussed in some detail. Finally, the inter-relationship between magnesium and the mitochondrial enzyme systems concerned with oxidative phosphorylation is stressed. The early detection of magnesium deficiency by routine methods is imperative for the prevention of abnormal cardiac metabolism and the maintenance of the functional and structural integrity of cardiac muscle during anaesthesia.


Effect of doxapram on control of breathing in cats. The effects of doxapram infusion (0.25 mg.kg-1. min-1) were studied in cats anaesthetized with pentobarbitone (35 mg . kg-1 intraperitoneally). Cats were studied breathing 50 per cent oxygen and the responses to two concentrations of inspired carbon dioxide were measured. Doxapram infusion increased pulmonary ventilation by increasing both tidal volume and respiratory frequency, and also caused increases in the volume inspired in the first 0.5 second after the onset of an inspiration (V0.5) and the pressure generated in the airway 0.5 second after the onset of an inspiration when the airway had been occluded (P degrees 0.5). V 0.5, P degrees 0.5 and the mean inspiratory flow rate (VT/VI) were essentially equivalent indices of inspiratory drive. Doxapram infusion did not alter the effective impedance of the respiratory system (P degrees 0.5/V 0.5). Doxapram infusion increased the ventilatory response to carbon dioxide. The slope of the ventilatory response to carbon dioxide was increased and the response line was shifted to the left. We conclude that the increase in pulmonary ventilation caused by doxapram infusion is due almost entirely to increased inspiratory neuromuscular drive (P degrees 0.5).


Efficacy of helium--oxygen mixtures in the management of severe viral and post-intubation croup. An appreciable number of children with viral or post-intubation croup progress to respiratory failure necessitating an artificial airway. We report seven such patients with critical airway narrowing in whom we reduced the work of breathing by developing helium rather than air as a carrier gas for oxygen. Assessment of patients by a croup-scoring system and blood gas analysis suggests helium-oxygen mixtures to be a useful alternative to intervention with tracheostomy or tracheal intubation. The rationale and limitations of this treatment are discussed.


Rectal methohexitone for induction of anaesthesia in children. Rectal induction of anaesthesia using ten per cent methohexitone is a safe and effective method for young children. It is particularly applicable to the child three months to four years of age. Twenty-five mg.kg-1 of methohexitone should be given and the child should be observed continuously by the anaesthetist until he falls asleep. Equipment to establish an artificial airway and to ventilate the lungs should be immediately at hand. The use of rectal methohexitone does not significantly delay immediate or late recovery after short (30-minute) surgical procedures.


Chronic pain syndromes and their treatment. II. Trigger points. Trigger points are distinct areas of focal hyperirritability which give rise to areas of refered pain in well-defined areas of the musculo-skeletal system, sometimes remote from the point itself and not related to it by anatomically definable pathways. While the vast majority of pain manifestations from trigger points are related to the musculo-skeletal system, this need not be invariably so, as has been demonstrated in two of the cases cited, where injection of trigger points in the neck relieved chronic tinnitus. In all manifestations of chronic pain it is recommended that a diligent search be made for such trigger points.


Foetal monitoring during general surgery: a case report. A case is reported in which the foetal heart was monitored by a Doppler apparatus during and after an operation on the kidney in a patient who was 27 weeks pregnant. This monitoring proved useful in detecting alterations of foetal heart rate which occurred during positioning of the patient.


Anaesthesia for facial rhytidectomy.

Anaesthesia for facial rhytidectomy. Observations on anaesthesia for facial rhytidectomy in 200 patients, without tracheal intubation or artificial ventilation, are reported in this survey.


A "last ditch" airway.

A "last ditch" airway. In a patient whose airway is in jeopardy after unsuccessful attempts at conservative measures to clear it and after failed attempts at intubation, the intravenous tubing connector spike may be considered as an emergency percutaneous tracheostomy device. It is readily available wherever physicians have intravenous solutions at hand. It is inserted through the cricothyroid space with the help of a scalpel blade or other sharp instrument such as a pair of scissors. A severed spike can be as easily carried in a pocket, purse or medical bag as can an intravenous cannula. A number 11 scalpel blade fits neatly between two credit cards. The shape of the spike makes it fortuitously adaptable to intermittent positive pressure ventilation by mouth or standard resuscitation equipment. If the patient is otherwise well enough, it is of sufficient bore to allow spontaneous respiration. I have been fortunate not to have had the opportunity to use this device in an emergency situation as of the time of the submission of this paper.


Effects of apomorphine on thermoregulatory responses of rats to different ambient temperatures. Either systemic or central administration of apomorphine produced dose-related decreases in rectal temperature at ambient temperatures (Ta) of 8 and 22 degrees C in rats. At Ta = 8 degrees C, the hypothermia was brought about by a decrease in metabolic rate (M). At Ta = 22 degrees C, the hypothermia was due to an increase in mean skin temperature, an increase in respiratory evaporative heat loss (Eres) and a decrease in M. This increased mean skin temperature was due to increased tail and foot skin temperatures. However, at Ta = 29 degrees C, apomorphine produced increased rectal temperatures due to increased M and decreased Eres. Moreover, the apomorphine-induced hypothermia or hyperthermia was antagonized by either haloperidol or 6-hydroxydopamine, but not by 5,6-dihydroxytryptamine. The data indicate that apomorphine acts on dopamine neurons within brain, with both pre- and post-synaptic sites of action, to influence body temperature.


Effect of acute exercise on tissue free fatty acids in untrained rats. The effects of a single bout of swimming on free fatty acids (FFA) in adipose tissue, heart, skeletal muscle, and serum were examined. Surprisingly, in previously untrained rats, FFA were elevated (P less than 0.001) in epididymal, inguinal, and retroperitoneal adipose depots 48 h after a 2-h swim. FFA in the three fat depots returned to resting levels 96 h after exercise. In heart, soleus, and fast-red fibers of the quadriceps, FFA remained elevated (P less than 0.01) for as long as 72 h after the 2-h swim. Serum FFA were still elevated (P less than 0.001) 96 h after swimming but not after 168 h. These results provide evidence that the rise in FFA is an acute effect of exercise and not a cellular adaptation resulting from daily episodes of lipolysis induced by exercise training. In a separate experiment, involving the adaptive response to endurance exercise, adipocytes from epididymal, inguinal, and retroperitoneal depots were reduced in size (P less than 0.001) to approximately the same degree. These results provide evidence that adipocytes from each depot contribute equally in meeting the energy needs of muscle during repeated bouts of endurance exercise.


Electrical coupling in rat myometrium during pregnancy. Gap junctions were found in rat myometrium only during parturition of abortion. A comparison was made between the values of the length constants obtained from longitudinally cut strips of rat myometrium at the midterm stage of pregnancy and during parturition. No significant difference was found between these values. No significant difference was found between length constants measured in myometrium from rats near term (22 days) and those during parturition, or between midterm myometrium and myometrium taken from animals aborting at midterm following ovariectomy. It was concluded that the appearance of gap junctions in parturient myometrium does not alter the spread of passive current in the longitudinal axis of the cells in these tissues. It is suggested that gap junctions are not required for spread of passive current, and that other structures may provide an alternate path.


Effect of allyl isothiocyanate on plasma and urinary concentrations of some biochemical entities in the rat. Allyl isothiocyanate (AITC) is a constituent of several plants of the family Cruciferae that are commonly used as food. This study investigated the effect of feeding AITC to male Sprague-Dawley rats on their plasma glucose and uric acid levels as well as on the urinary concentrations of glucose, 17-ketosteroids (17-KS), creatinine, and uric acid. Other test compounds included were thyroxine (T4) and thiouracil (TU). AITC caused a highly significant (P smaller than or equal to 0.01) depression in the plasma glucose and uric acid levels compared with the control. TU caused a significant depression only of the plasma glucose. T4, on the other hand, significantly increased the levels of both glucose and uric acid. The AITC-treated rats voided twice as much urine as the controls or those receiving TU or injected with T4. The 24-h excretion of glucose, uric acid, and creatinine was significantly (P smaller than or equal to 0.01) higher in animals fed AITC than in those consuming the control diet, while the excretion of 17-KS was significantly lower. Results on an equal urine volume basis showed that differences in the excretion of glucose and creatinine were related to differences in the urine volume. TU significantly depressed excretion of all the compounds but glucose. The effect of T4 on the excretion of 17-KS and uric acid resembled that of AITC and TU, thus showing that these compounds depressed the androgenic function of the animal.


Apparent volume of the biliary tree in the dog. The apparent volume of the biliary tree (ABV) in the dog was determined by measuring the mean biliary transit time of injected [14C]taurocholate ([14C]TC). After bolus injection of [14C]TC, entry of bile salt into the lumen of the biliary tree is signaled by an increase in bile flow. The volume of bile collected at the common duct from onset of choleresis until maximal concentration of 14C radioactivity is reached in bile minus the calculated quantity of bile that contains radioactivity and the cannula volume yields a value for the volume of the biliary tree present just prior to injection of [14C]TC. The mean value for ABV in 19 dogs was 2.49 +/- 0.65 microL/g liver (mean +/- SD).


Factors affecting the encapsulation of drugs within liposomes. The reported efficiencies of drug encapsulation into liposomes range from less than 0.1% to more than 10% per micromole phospholipid, depending on the nature of the drug and of the liposome employed. We have sought to investigate some of the factors which control the efficiency of drug encapsulation. We have found that most polar drugs are sequestered within the internal aqueous compartment of the liposomes, while nonpolar drugs can bind to the liposome membrane in addition to being sequestered, thus accounting for their higher efficiencies of encapsulation. The encapsulation of nonpolar drugs, but not of polar drugs, is very sensitive to the physical characteristics of the liposome membrane; in particular, a fluid membrane favors the efficient encapsulation of nonpolar compounds. The drug cytosine arabinoside is anomalous in that this highly polar compound seems to interact with the liposome membrane at physiological conditions of pH and ionic strength, thus allowing it to be encapsulated with high efficiency.


Clinical use of blood, blood components and blood products. The goal of modern transfusion therapy is to provide appropriate replacement therapy with blood components as opposed to whole blood for patients with specific hematologic deficiencies. A prerequisite of component therapy is, therefore, correct identification of the deficiency. Appropriate use of components avoids many of the hazards associated with the use of whole blood, and at the same time makes maximal use of this valuable resource. Blood components separated from whole blood soon after collection and appropriately stored can, in combination, provide all the factors present in fresh whole blood. Red cell concentrates prepared from multiple packs have a hematocrit of approximately 70%. They may be stored for up to 3 weeks at 4 degrees C and are recommended for most situations requiring red cell transfusions. Platelet concentrates, which can be stored for up to 72 hours at 22 degrees C, may be used for thrombocytopenic patients. Fresh frozen plasma, stored plasma, cryoprecipitated factor VIII, factor VIII concentrate and factor IX complex concentrate are available for the proper treatment of patients with hemorrhagic disorders due to coagulation factor deficiencies. Similarly, albumin and immune serum globulin are available for their oncotic and antibody properties respectively. Thus, the availability and appropriate use of the various blood products allows not only optimal transfusion therapy for each patient, but also fuller utilization of national blood resources.