Discriminative stimulus effects of amphetamine and pentobarbitone separately and as mixtures in rats

Abstract

The discriminative effect of a mixture of (+)-amphetamine plus pentobarbitone was investigated to characterize behavioural control by a compound interoceptive stimulus. A two-bar drug discrimination procedure with food reinforcement was used. The role of training dose was assessed by keeping the dose of (+)-amphetamine constant at 0.4mg/kg (SC) and progressively increasing that of pentobarbitone from 5mg/kg to 20mg/kg (SC). Initially stimulus control was attributable to (+)-amphetamine but as the dose of pentobarbitone was increased, stimulus control switched entirely to pentobarbitone. The reduced response to (+)-amphetamine after training in compound with the larger doses of pentobarbitone was attributed to overshadowing of a relatively weak (+)-amphetamine stimulus by a more salient pentobarbital stimulus. There was partial generalization when either component drug was given at the same dose as in the mixture, and almost complete generalization at larger doses of each component; in contrast, there was little cross-generalization between (+)-amphetamine and pentobarbitone in rats trained with either drug alone. The findings suggested that components of the compound stimulus were perceived and processed separately rather than being blended into a new and distinct stimulus. Tests for generalization to quipazine, phencyclidine or morphine suggested that the compound stimulus produced by the mixture was no less specific than the stimuli produced by each of the component drugs. Rules governing discrimination of the abused mixture of (+)-amphetamine plus pentobarbitone appeared generally similar to those found in previous studies with non-abused mixtures of nicotine and midazolam.