The discriminative stimulus effects of mecamylamine in nicotine-treated and untreated rhesus monkeys

摘要

The extent to which chronic nicotine treatment can alter the effects of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine, and whether those effects can be attenuated by nicotine has not been clearly established in the literature. Here, the discriminative stimulus effects of mecamylamine were compared in one group of rhesus monkeys receiving continuous infusion of nicotine base (5.6 mg/kg/day s.c.) and another group of monkeys not receiving nicotine treatment. Both groups responded under a fixed ratio 5 schedule of stimulus-shock termination. Stimulus control was obtained at doses of 1.78 mg/kg of mecamylamine in monkeys receiving continuous nicotine and 5.6 mg/kg of mecamylamine in monkeys not receiving continuous nicotine treatment. Nicotine did not attenuate the discriminative stimulus effects of mecamylamine in either group. Discontinuation of continuous nicotine produced responding on the mecamylamine lever within 24 h in some but not all monkeys. This may indicate a qualitative difference in the discriminative stimulus effects of mecamylamine across groups, perhaps reflecting antagonism of nicotine and nicotine withdrawal in monkeys receiving continuous nicotine. The failure of nicotine to reverse the effects of mecamylamine is consistent with a non-competitive interaction at nAChRs and indicates that mecamylamine-induced withdrawal cannot be readily modified by nicotine.