Influencing the specificity of drug mixture discriminations by varying the training procedure

Studies of the discriminative stimulus effects of drug mixtures provide an approach to polydrug abuse and to studies on single drugs with multiple effects. The experiments described here investigated whether the use of the AND-OR procedure increases the specificity of drug mixture discriminations. Rats were trained to discriminate a mixture of nicotine (0.4 mg/ kg) plus midazolam (0.2 mg/kg) from saline (AND-discrimination, n = 10) or to discriminate the same mixture from its component drugs alone (AND-OR discrimination, n = 10). The studies used two-lever operant procedures with a tandem variable interval 1 min fixed ratio 10 (FR 10) schedule of food reinforcement. Under AND-discrimination conditions, there was partial generalization to amphetamine and pentobarbitone when each drug was administered singly. With the AND-OR-discrimination, there was no generalization to amphetamine and partial generalization to pentobarbitone. In 'single substitution' tests, pentobarbitone or amphetamine was co-administered with the training doses of nicotine and midazolam, respectively; there was full generalization in the AND-discrimination and no generalization under AND-OR conditions. In 'dual substitution' tests, mixtures of amphetamine plus pentobarbitone produced full generalization under AND-discrimination conditions, and partial generalization in the AND-OR procedure. Wherever comparisons were made, generalization was less under AND-OR- than under the AND-discrimination procedure, confirming that the AND-OR procedure can increase the specificity of discriminations based on drug mixtures. The similarity with findings reported previously for training with mixtures of amphetamine plus pentobarbitone suggests that this may reflect a general principle rather than a phenomenon restricted to particular training drugs.