Mecamylamine Reverses the Effects of Cytisine on the Oral Self-administration of Ethanol in Rats.

Introduction: It has been suggested that nicotinic acetylcholine receptors (nAchRs) expressed in the ventral tegmental area (VTA) and the nucleus accumbens (nAcc) modulate the effects of drug abuse. This research assessed the effects of intra-accumbal administration of the nAchR antagonist (mecamylamine) and agonist (cytisine) on the operant oral self-administration of ethanol (EtOH) in rats. Methods: Male Wistar rats were water-deprived for 24 h and then trained to lever-press for EtOH reinforcement on a fixed-ratio 1 (FR1) schedule for three sessions. After that, the number of responses in the FR schedule increased to 3 until the response rate remained stable at 80%. After this training, the rats received an intra-accumbal injection of the nAchR antagonist, mecamylamine (0.0, 1.25, 2.5, and 5.0 μg), then nAchR agonist, cytisine (0.0, 0.8, 1.6, and 3.2 μg) or the combination of mecamylamine (0.0, 1.25, 2.5, and 5.0 μg) and cytisine (3.2 μg) before being provided access to EtOH on a FR3 schedule. Results: The data showed that intra-accumbal administration of mecamylamine reduced operant oral self-administration of EtOH, whereas cytisine increased operant oral self-administration of EtOH. This effect was reversed by mecamylamine. Conclusion: These findings suggest that nAchRs in the nAcc may modulate the operant oral self-administration of EtOH in rats.