Ea. Mariathasan et Ip. Stolerman, DISCRIMINATION OF AGONIST-ANTAGONIST MIXTURES - EXPERIMENTS WITH NICOTINE PLUS MECAMYLAMINE, Behavioural pharmacology, 4(6), 1993, pp. 555-561
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.