In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function
Paul D. Callaghan, W. Anthony Owens, Martin A. Javors, Teresa A. Sanchez, David J. Jones, Rodney J. Irvine, Lynette C. Daws
Department of Psychiatry & Behavioral Sciences
Department of Cellular & Integrative Physiology
p-Methoxyamphetamine (PMA) has been implicated in fatalities as a result of 'ecstasy' (MDMA) overdose worldwide. Like MDMA, acute effects are associated with marked changes in serotonergic neurotransmission, but the long-term effects of PMA are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on in vitro measures of neurodegeneration: serotonin (5-HT) uptake, 5-HT transporter (SERT) density and 5-HT content in the hippocampus, and compare with effects on in vivo 5-HT clearance. Male rats received PMA, MDMA (4 or 15 mg/kg s.c., twice daily) or vehicle for 4 days and 2 weeks later indices of SERT function were measured. [3H]5-HT uptake into synaptosomes and [3H]cyanoimipramine binding to the SERT were significantly reduced by both PMA and MDMA treatments. 5-HT content was reduced in MDMA-, but not PMA-treatment. In contrast, clearance of locally applied 5-HT measured in vivo by chronoamperometry was only reduced in rats treated with 15 mg/kg PMA. The finding that 5-HT clearance in vivo was unaltered by MDMA treatment suggests that in vitro measures of 5-HT axonal degeneration do not necessarily predict potential compensatory mechanisms that maintain SERT function under basal conditions.
Journal of neurochemistry
3, 4-methylenedioxymethamphetamine
Chronoamperometry
Para-methoxyamphetamine
Serotonin transporter
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Midomafetamine Medicine and Dentistry 100%
MDMA Pharmacology, Toxicology and Pharmaceutical Science 100%
Clearance Medicine and Dentistry 57%
In Vivo Neuroscience 57%
Therapeutic Procedure Medicine and Dentistry 42%
Rat Pharmacology, Toxicology and Pharmaceutical Science 42%
Serotonin Medicine and Dentistry 28%
In Vitro Medicine and Dentistry 28%
Callaghan, P. D., Owens, W. A., Javors, M. A., Sanchez, T. A., Jones, D. J., Irvine, R. J., & Daws, L. C. (2007). In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function. Journal of neurochemistry, 100(3), 617-627. https://doi.org/10.1111/j.1471-4159.2006.04247.x
In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function. / Callaghan, Paul D.; Owens, W. Anthony; Javors, Martin A. et al.
In: Journal of neurochemistry, Vol. 100, No. 3, 02.2007, p. 617-627.
Callaghan, PD, Owens, WA, Javors, MA, Sanchez, TA, Jones, DJ, Irvine, RJ & Daws, LC 2007, 'In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function', Journal of neurochemistry, vol. 100, no. 3, pp. 617-627. https://doi.org/10.1111/j.1471-4159.2006.04247.x
Callaghan PD, Owens WA, Javors MA, Sanchez TA, Jones DJ, Irvine RJ et al. In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function. Journal of neurochemistry. 2007 Feb;100(3):617-627. doi: 10.1111/j.1471-4159.2006.04247.x
Callaghan, Paul D. ; Owens, W. Anthony ; Javors, Martin A. et al. / In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function. In: Journal of neurochemistry. 2007 ; Vol. 100, No. 3. pp. 617-627.
@article{e99225a4e99540b39302aefea9f23ec7,
title = "In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function",
abstract = "p-Methoxyamphetamine (PMA) has been implicated in fatalities as a result of 'ecstasy' (MDMA) overdose worldwide. Like MDMA, acute effects are associated with marked changes in serotonergic neurotransmission, but the long-term effects of PMA are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on in vitro measures of neurodegeneration: serotonin (5-HT) uptake, 5-HT transporter (SERT) density and 5-HT content in the hippocampus, and compare with effects on in vivo 5-HT clearance. Male rats received PMA, MDMA (4 or 15 mg/kg s.c., twice daily) or vehicle for 4 days and 2 weeks later indices of SERT function were measured. [3H]5-HT uptake into synaptosomes and [3H]cyanoimipramine binding to the SERT were significantly reduced by both PMA and MDMA treatments. 5-HT content was reduced in MDMA-, but not PMA-treatment. In contrast, clearance of locally applied 5-HT measured in vivo by chronoamperometry was only reduced in rats treated with 15 mg/kg PMA. The finding that 5-HT clearance in vivo was unaltered by MDMA treatment suggests that in vitro measures of 5-HT axonal degeneration do not necessarily predict potential compensatory mechanisms that maintain SERT function under basal conditions.",
keywords = "3, 4-methylenedioxymethamphetamine, Chronoamperometry, Neurodegeneration, Para-methoxyamphetamine, Serotonin, Serotonin transporter",
author = "Callaghan, {Paul D.} and Owens, {W. Anthony} and Javors, {Martin A.} and Sanchez, {Teresa A.} and Jones, {David J.} and Irvine, {Rodney J.} and Daws, {Lynette C.}",
journal = "Journal of Neurochemistry",
T1 - In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function
AU - Callaghan, Paul D.
AU - Owens, W. Anthony
AU - Javors, Martin A.
AU - Sanchez, Teresa A.
AU - Jones, David J.
AU - Irvine, Rodney J.
AU - Daws, Lynette C.
N2 - p-Methoxyamphetamine (PMA) has been implicated in fatalities as a result of 'ecstasy' (MDMA) overdose worldwide. Like MDMA, acute effects are associated with marked changes in serotonergic neurotransmission, but the long-term effects of PMA are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on in vitro measures of neurodegeneration: serotonin (5-HT) uptake, 5-HT transporter (SERT) density and 5-HT content in the hippocampus, and compare with effects on in vivo 5-HT clearance. Male rats received PMA, MDMA (4 or 15 mg/kg s.c., twice daily) or vehicle for 4 days and 2 weeks later indices of SERT function were measured. [3H]5-HT uptake into synaptosomes and [3H]cyanoimipramine binding to the SERT were significantly reduced by both PMA and MDMA treatments. 5-HT content was reduced in MDMA-, but not PMA-treatment. In contrast, clearance of locally applied 5-HT measured in vivo by chronoamperometry was only reduced in rats treated with 15 mg/kg PMA. The finding that 5-HT clearance in vivo was unaltered by MDMA treatment suggests that in vitro measures of 5-HT axonal degeneration do not necessarily predict potential compensatory mechanisms that maintain SERT function under basal conditions.
AB - p-Methoxyamphetamine (PMA) has been implicated in fatalities as a result of 'ecstasy' (MDMA) overdose worldwide. Like MDMA, acute effects are associated with marked changes in serotonergic neurotransmission, but the long-term effects of PMA are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on in vitro measures of neurodegeneration: serotonin (5-HT) uptake, 5-HT transporter (SERT) density and 5-HT content in the hippocampus, and compare with effects on in vivo 5-HT clearance. Male rats received PMA, MDMA (4 or 15 mg/kg s.c., twice daily) or vehicle for 4 days and 2 weeks later indices of SERT function were measured. [3H]5-HT uptake into synaptosomes and [3H]cyanoimipramine binding to the SERT were significantly reduced by both PMA and MDMA treatments. 5-HT content was reduced in MDMA-, but not PMA-treatment. In contrast, clearance of locally applied 5-HT measured in vivo by chronoamperometry was only reduced in rats treated with 15 mg/kg PMA. The finding that 5-HT clearance in vivo was unaltered by MDMA treatment suggests that in vitro measures of 5-HT axonal degeneration do not necessarily predict potential compensatory mechanisms that maintain SERT function under basal conditions.
KW - 3, 4-methylenedioxymethamphetamine
KW - Chronoamperometry
KW - Neurodegeneration
KW - Para-methoxyamphetamine
KW - Serotonin
KW - Serotonin transporter
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry