Rewarding effects elicited by cocaine microinjections into the ventral tegmental area of C57BL/6 mice: involvement of dopamine D1 and serotonin1B receptors
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The role of ventral tegmental area (VTA) in mediating the rewarding effects of cocaine has not been extensively studied.
We used the intracranial self-administration (ICSA) procedure to assess the involvement of the VTA in the rewarding effects of cocaine, and the effect of dopamine (DA) D1- and serotonin (5-HT)1B-receptor antagonists on ICSA of cocaine.
Adult male C57BL/6 mice were stereotaxically implanted, unilaterally, with a guide cannula either 1.5 or 2.3 mm above the VTA. After 1 week, mice were trained to discriminate between the two arms of a Y-maze over seven daily sessions, one arm being reinforced by intracranial cocaine microinjections. Starting from session 8, the D1 and 5-HT1B-receptor antagonists were injected IP pre-test each day over five consecutive sessions.
Mice injected into the VTA rapidly exhibited a preference for the cocaine-reinforced arm, whatever the dose of cocaine available (30 pmol or 150 pmol per injection), reaching optimum ICSA performance within 5 days. In contrast, mice injected 0.8 mm above the VTA did not discriminate between the arms of the maze and performed at random, except for one subject. Once the ICSA response was acquired, systemic pre-injections of either the D1 (SCH23390; 25 μg/kg IP) or 5-HT1B (GR127935; 0.5 mg/kg IP) antagonist disrupted this behavior. Replacement of each antagonist by vehicle led to the reinstatement of intra-VTA cocaine self-administration.
The results of the present study suggest that VTA neurons play a critical role in mediating the rewarding effects of acute cocaine and that both D1 and 5-HT1B receptors modulate these effects.
KeywordsVentral tegmental area Intracranial self-administration Cocaine reinforcement 5-HT receptors Dopamine D receptors GR127935 SCH23390
We would like to thank Mrs. L. Decorte and D. Panzeri for their excellent technical assistance and Dr. T.P. Durkin for correction of the English text and useful discussions. This investigation was supported by the CNRS (UMR 5106).
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