The discriminative stimulus properties of cocaine: Effects of microinfusion of cocaine, a 5-HT(1A) agonist or antagonist, into the ventral tegmental area
Richard De La Garza, Patrick Michael Callahan, Kathryn A. Cunningham
Serotonin (5-HT) afferents may modulate the dopamine mesoaccumbens circuit, which has been shown to be critically involved in the locomotor stimulatory, discriminative stimulus, and rewarding properties of cocaine. In the present study, we investigated the role of 5-HT(1A) receptors in the ventral tegmental area (VTA) in mediating the discriminative stimulus effects of cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task. After acquiring the cocaine-saline discrimination, rats were stereotaxically implanted with bilateral guide cannulae into the VTA or adjacent substantia nigra reticulata (SNR). Intraperitoneal administration of cocaine (0.625-10 mg/kg) produced a dose-related increase in drug-lever responding. Both intra-VTA and intra-SNR infusion of cocaine (12.5-50 μg/0.5 μl/side) engendered primarily saline-like responding. Microinjection of the 5-HT(1A) agonist 8-hydroxy-2-(di-N-propylamino) tetralin (DPAT; 0.1-10 μg/0.5 μl/side) or the 5-HT(1A) antagonist WAY 100635 (0.01-1.0 μg/0.5 μl/side) into the VTA or SNR did not substitute for the systemic cocaine cue. Further, intra-VTA or intra-SNR DPAT or WAY 100635 in combination with systemic doses of cocaine did not alter (i.e., attenuate or potentiate) the systemic cocaine cue. Overall, these data indicate that 5-HT(1A) receptors in the VTA do not mediate or modulate the discriminative stimulus effects of cocaine in the rat.
Published - May 28 1998
Serotonin Receptor Agonists
Serotonin Antagonists
Ventral Tegmental Area
Receptor, Serotonin, 5-HT1A
Microinjections
5-HT(1A) receptor
8-Hydroxy-2-(di-N-propylamino) tetralin (DPAT)
Drug discrimination
WAY 100635
De La Garza, R., Callahan, P. M., & Cunningham, K. A. (1998). The discriminative stimulus properties of cocaine: Effects of microinfusion of cocaine, a 5-HT(1A) agonist or antagonist, into the ventral tegmental area. Psychopharmacology, 137(1), 1-6. https://doi.org/10.1007/s002130050586
The discriminative stimulus properties of cocaine : Effects of microinfusion of cocaine, a 5-HT(1A) agonist or antagonist, into the ventral tegmental area. / De La Garza, Richard; Callahan, Patrick Michael; Cunningham, Kathryn A.
In: Psychopharmacology, Vol. 137, No. 1, 28.05.1998, p. 1-6.
De La Garza, R, Callahan, PM & Cunningham, KA 1998, 'The discriminative stimulus properties of cocaine: Effects of microinfusion of cocaine, a 5-HT(1A) agonist or antagonist, into the ventral tegmental area', Psychopharmacology, vol. 137, no. 1, pp. 1-6. https://doi.org/10.1007/s002130050586
De La Garza R, Callahan PM, Cunningham KA. The discriminative stimulus properties of cocaine: Effects of microinfusion of cocaine, a 5-HT(1A) agonist or antagonist, into the ventral tegmental area. Psychopharmacology. 1998 May 28;137(1):1-6. https://doi.org/10.1007/s002130050586
De La Garza, Richard ; Callahan, Patrick Michael ; Cunningham, Kathryn A. / The discriminative stimulus properties of cocaine : Effects of microinfusion of cocaine, a 5-HT(1A) agonist or antagonist, into the ventral tegmental area. In: Psychopharmacology. 1998 ; Vol. 137, No. 1. pp. 1-6.
@article{9d8f84f31cfa41fd89a59012190d2e6d,
title = "The discriminative stimulus properties of cocaine: Effects of microinfusion of cocaine, a 5-HT(1A) agonist or antagonist, into the ventral tegmental area",
abstract = "Serotonin (5-HT) afferents may modulate the dopamine mesoaccumbens circuit, which has been shown to be critically involved in the locomotor stimulatory, discriminative stimulus, and rewarding properties of cocaine. In the present study, we investigated the role of 5-HT(1A) receptors in the ventral tegmental area (VTA) in mediating the discriminative stimulus effects of cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task. After acquiring the cocaine-saline discrimination, rats were stereotaxically implanted with bilateral guide cannulae into the VTA or adjacent substantia nigra reticulata (SNR). Intraperitoneal administration of cocaine (0.625-10 mg/kg) produced a dose-related increase in drug-lever responding. Both intra-VTA and intra-SNR infusion of cocaine (12.5-50 μg/0.5 μl/side) engendered primarily saline-like responding. Microinjection of the 5-HT(1A) agonist 8-hydroxy-2-(di-N-propylamino) tetralin (DPAT; 0.1-10 μg/0.5 μl/side) or the 5-HT(1A) antagonist WAY 100635 (0.01-1.0 μg/0.5 μl/side) into the VTA or SNR did not substitute for the systemic cocaine cue. Further, intra-VTA or intra-SNR DPAT or WAY 100635 in combination with systemic doses of cocaine did not alter (i.e., attenuate or potentiate) the systemic cocaine cue. Overall, these data indicate that 5-HT(1A) receptors in the VTA do not mediate or modulate the discriminative stimulus effects of cocaine in the rat.",
keywords = "5-HT(1A) receptor, 8-Hydroxy-2-(di-N-propylamino) tetralin (DPAT), Cocaine, Dopamine, Drug discrimination, Microinjection, Serotonin, Ventral tegmental area, WAY 100635",
author = "{De La Garza}, Richard and Callahan, {Patrick Michael} and Cunningham, {Kathryn A.}",
T1 - The discriminative stimulus properties of cocaine
T2 - Effects of microinfusion of cocaine, a 5-HT(1A) agonist or antagonist, into the ventral tegmental area
AU - De La Garza, Richard
AU - Callahan, Patrick Michael
AU - Cunningham, Kathryn A.
N2 - Serotonin (5-HT) afferents may modulate the dopamine mesoaccumbens circuit, which has been shown to be critically involved in the locomotor stimulatory, discriminative stimulus, and rewarding properties of cocaine. In the present study, we investigated the role of 5-HT(1A) receptors in the ventral tegmental area (VTA) in mediating the discriminative stimulus effects of cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task. After acquiring the cocaine-saline discrimination, rats were stereotaxically implanted with bilateral guide cannulae into the VTA or adjacent substantia nigra reticulata (SNR). Intraperitoneal administration of cocaine (0.625-10 mg/kg) produced a dose-related increase in drug-lever responding. Both intra-VTA and intra-SNR infusion of cocaine (12.5-50 μg/0.5 μl/side) engendered primarily saline-like responding. Microinjection of the 5-HT(1A) agonist 8-hydroxy-2-(di-N-propylamino) tetralin (DPAT; 0.1-10 μg/0.5 μl/side) or the 5-HT(1A) antagonist WAY 100635 (0.01-1.0 μg/0.5 μl/side) into the VTA or SNR did not substitute for the systemic cocaine cue. Further, intra-VTA or intra-SNR DPAT or WAY 100635 in combination with systemic doses of cocaine did not alter (i.e., attenuate or potentiate) the systemic cocaine cue. Overall, these data indicate that 5-HT(1A) receptors in the VTA do not mediate or modulate the discriminative stimulus effects of cocaine in the rat.
AB - Serotonin (5-HT) afferents may modulate the dopamine mesoaccumbens circuit, which has been shown to be critically involved in the locomotor stimulatory, discriminative stimulus, and rewarding properties of cocaine. In the present study, we investigated the role of 5-HT(1A) receptors in the ventral tegmental area (VTA) in mediating the discriminative stimulus effects of cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task. After acquiring the cocaine-saline discrimination, rats were stereotaxically implanted with bilateral guide cannulae into the VTA or adjacent substantia nigra reticulata (SNR). Intraperitoneal administration of cocaine (0.625-10 mg/kg) produced a dose-related increase in drug-lever responding. Both intra-VTA and intra-SNR infusion of cocaine (12.5-50 μg/0.5 μl/side) engendered primarily saline-like responding. Microinjection of the 5-HT(1A) agonist 8-hydroxy-2-(di-N-propylamino) tetralin (DPAT; 0.1-10 μg/0.5 μl/side) or the 5-HT(1A) antagonist WAY 100635 (0.01-1.0 μg/0.5 μl/side) into the VTA or SNR did not substitute for the systemic cocaine cue. Further, intra-VTA or intra-SNR DPAT or WAY 100635 in combination with systemic doses of cocaine did not alter (i.e., attenuate or potentiate) the systemic cocaine cue. Overall, these data indicate that 5-HT(1A) receptors in the VTA do not mediate or modulate the discriminative stimulus effects of cocaine in the rat.
KW - 5-HT(1A) receptor
KW - 8-Hydroxy-2-(di-N-propylamino) tetralin (DPAT)
KW - Cocaine
KW - Drug discrimination
KW - Microinjection
KW - Serotonin
KW - Ventral tegmental area
KW - WAY 100635