Involvement of local serotonin-2A but not serotonin-1B receptors in the reinforcing effects of ethanol within the posterior ventral tegmental area of female Wistar rats

Rationale: Previous studies indicated that ethanol could be self-infused into the posterior ventral tegmental area (p-VTA) and that activation of local serotonin-3 (5-HT₃) receptors was involved. 5-HT_1B and 5-HT_2A receptors are involved in the effects of 5-HT and ethanol on VTA dopamine neurons. Objective: The current study used the intracranial self-administration (ICSA) procedure to determine the involvement of local 5-HT_1B and 5-HT_2A receptors in the self-infusion of ethanol into the p-VTA. Materials and methods: Female Wistar rats were implanted unilaterally with a guide cannula aimed at the p-VTA. Seven days after surgery, rats were placed into the two-lever operant conditioning chambers for ICSA tests. The tests consisted of four acquisition sessions with self-infusion of 200 mg% ethanol alone, two or three sessions with co-infusion of the 5-HT _1B antagonist GR 55562 (10, 100, or 200 μM) or the 5-HT _2A antagonist R-96544 (10, 100, or 200 μM) with 200 mg% ethanol, and one final session with 200 mg% ethanol alone. Results: During the acquisition sessions, all rats readily self-infused ethanol and discriminated the active from inactive lever. Co-infusion of GR 55562, at all three doses, had no effect on the self-infusion of ethanol. In contrast, co-infusion of R-96544, at the two higher doses, attenuated responding on the active lever for ethanol infusion (p∈<∈0.05). Conclusion: The results suggest that the reinforcing effects of ethanol within the p-VTA are modulated, at least in part, by activation of local 5-HT_2A, but not 5-HT_1B, receptors.