TY - JOUR
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 M.
AU - Cunningham, Kathryn A.
N1 - Funding Information:
&p.2: wledgements The research described herein was supported by National Institute on Drug Abuse grants DA 05638 (R. D.) and DA 05708, DA 06511 and DA 00260 (K. A. C.). The authors would like to thank Dr. Andrew McCreary for his insightful comments on this manuscript and Ms. Wilma Frye for her assistance in its preparation. We also wish to express sincere appreciation to Wyeth Research Ltd (UK) for their generous gift of WAY 100635. Animals used in this study were maintained in accordance with the guidelines of the Institutional Animal Care and Use Committee of the University of Texas Medical Branch, and the “Guide for the Care and Use of Laboratory Animals” (Department of Health and Human Services, National Institutes of Health, Publication No. 85-23, revised 1985).
PY - 1998
Y1 - 1998
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 - Dopamine
KW - Drug discrimination
KW - Microinjection
KW - Serotonin
KW - Ventral tegmental area
KW - WAY 100635
UR - http://www.scopus.com/inward/record.url?scp=0031976654&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031976654&partnerID=8YFLogxK
U2 - 10.1007/s002130050586
DO - 10.1007/s002130050586
M3 - Article
C2 - 9631950
AN - SCOPUS:0031976654
SN - 0033-3158
VL - 137
SP - 1
EP - 6
JO - Psychopharmacology
JF - Psychopharmacology
IS - 1
ER -