Functional relationships, previous history and the discrimination of a drug mixture in rats

These experiments aim to probe the role of different functional relationships between drugs, responses and reinforcers in studies on the discrimination of drug mixtures. Two-lever discriminations based on mixtures of (+)-amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) have been compared in three groups of rats (n = 8) trained to discriminate: (i) the mixture from saline, called the AND-discrimination; (ii) either the mixture, amphetamine or pentobarbitone from saline, the OR-discrimination; (iii) the mixture from either amphetamine or pentobarbitone, the AND-OR-discrimination. The rats were trained in a two-bar operant conditioning procedure with a tandem schedule of food reinforcement. The rats trained on the AND procedure acquired the discrimination more rapidly than the rats trained on the other two procedures, but after 60 training sessions, all discriminations were performed with similar (90-94%) accuracy. In rats trained under the AND and the OR procedures, there was full generalization from the mixture to the largest doses used of either amphetamine or pentobarbitone. In contrast, in rats trained under the AND-OR procedure, there was no generalization from the mixture to any dose of either drug separately. The training procedures for the OR and the AND-OR groups were changed to AND-discrimination training; the effects of the different previous histories were found to persist for a prolonged period, despite the fact that training conditions were now the same in all groups. The effects of the drugs on rates of responding were also influenced by the previous training history. Thus, using different training procedures to alter functional relationships can substantially and persistently influence the major characteristics of a discrimination based on a mixture of drugs.