Effects of serotonin-3 receptor antagonists on the intracranial self-administration of ethanol within the ventral tegmental area of Wistar rats

RATIONALE: Previous work from our laboratory indicated that Wistar rats will self-administer ethanol (EtOH) directly into the posterior ventral tegmental area (VTA) and that 5-HT(3) antagonists will inhibit EtOH-stimulated somatodendritic release of dopamine within the VTA. OBJECTIVES: The objective of this study was to use the intracranial self-administration procedure to determine the involvement of 5-HT(3)receptors in mediating the reinforcing effects of EtOH within the VTA, and to increase our understanding of central nervous system mechanisms involved in the rewarding effects of EtOH. METHODS: Adult female Wistar rats were stereotaxically implanted with guide cannulae aimed at the posterior VTA. After 1 week, rats were placed into standard two-lever experimental chambers for a total of seven sessions (4-h sessions separated by 48 h) and allowed to self-administer vehicle alone, a 5-HT(3) antagonist alone, 200 mg% EtOH alone, or combinations of 200 mg% EtOH with different concentrations of a 5-HT(3) antagonist ( n=6-9 per group). RESULTS: Throughout all seven sessions, Wistar rats self-infused more 200 mg% ETOH (25+/-5 infusions) than vehicle (5+/-4 infusions) or 5-HT(3) antagonist (6+/-4 infusions) ( P<0.05), and responded significantly more ( P<0.05) on the active than inactive lever (e.g., 50+/-12 vs 12+/-8 responses in session 1). Co-administration of 50 micro M or 100 micro M ICS 205,930 with 200 mg% EtOH completely prevented the acquisition and maintenance of EtOH self-infusion into the posterior VTA. Similarly, co-administration of either 25-100 micro M LY-278-584 or 10-100 micro M zacopride with 200 mg% EtOH completely blocked EtOH-maintained intracranial self-administration behavior. CONCLUSIONS: The results of this study suggest that the reinforcing effects of EtOH within the posterior VTA of Wistar rats require activation of local 5-HT(3) receptors.