DISCRIMINATION OF AGONIST-ANTAGONIST MIXTURES - EXPERIMENTS WITH NICOTINE PLUS MECAMYLAMINE

Discrimination of a mixture of an agonist plus an antagonist has been analysed by training rats to discriminate (-)-nicotine (0.32 mg/kg s.c .) from saline; in different groups of rats (n = 8), nicotine was admi nistered either alone or in combination with the non-competitive nicot ine antagonist mecamylamine (0.1-0.8 mg/kg s.c.). Rats were trained in a two-bar operant conditioning procedure with a tandem schedule of fo od reinforcement. After 50 sessions, rats trained with nicotine alone had acquired the discrimination with an accuracy of about 85 %. In com bination, mecamylamine blocked accuracy during acquisition in a dose-r elated manner. In generalization tests, rats trained with nicotine alo ne yielded a typical dose-response curve for nicotine (ED(50) = 0.082 mg/kg), without depression of response rate. In rats trained with nico tine plus 0.2 mg/kg of mecamylamine, the ED(50) for the discriminative effect of nicotine was lowered (ED(50) = 0.036 mg/kg), again without depression of response rate. In rats trained with nicotine plus 0.4-0. 8 mg/kg of mecamylamine, nicotine did not acquire stimulus control ove r behaviour (flat dose-response relationships), but in these animals, nicotine had a pronounced response rate-decreasing effect. These chara cteristics of discriminations based on nicotine plus mecamylamine diff ered substantially from those of previously described discriminations of nicotine plus midazolam, supporting the hypothesis that interaction s between the latter drugs were based on a behavioural mechanism (over shadowing) rather than on interactions at the level of receptors.