TRAINING DOSE AS A DECISIVE FACTOR FOR DISCRIMINATION OF A DRUG MIXTURE IN RATS

The impact of training dose on the characteristics of a discrimination maintained by a mixture of two dissimilar drugs has been investigated in order to refine this approach to the study of drug interactions. T hree groups of rats (n=10) were trained to discriminate mixtures of ()-amphetamine (0.2-0.8 mg/kg) plus pentobarbitone (5-20 mg/kg) from sa line, in a two-lever operant procedure with food reinforcement, with t he ratio of the doses held constant (amphetamine: pentobarbitone, 1 :2 5). Discriminations were acquired to an accuracy of 90-97%. There was full generalisation to amphetamine alone, but only in rats trained wit h mixtures of the smaller doses of the single drugs. There was partial generalisation when either apomorphine (50%) or nicotine (63%) was ad ministered alone, and the magnitude of these responses was inversely r elated to the dose of mixture used for training. Doses of pentobarbito ne half of those used for training produced little discriminative resp onse when administered alone to rats trained with the two smallest dos es of the mixture; the same doses of pentobarbitone increased response s to amphetamine or apomorphine in a more than additive manner Strikin gly, some doses of apomorphine and pentobarbitone that did not general ise when administered separately, produced full generalisation when ad ministered together, but only in rats trained with the smaller doses o f the mixture. In contrast, pentobarbitone did not enhance generalisat ion to nicotine in any group. It was concluded that, on the one hand, patterns of generalisation to single drugs followed an orderly pattern resembling those for discriminations established with single drugs. O n the other hand, there was a complex pattern of generalization from o ne mixture to another; thus, altering the doses of drugs used for trai ning markedly influenced discriminations of an abused drug mixture, bu t no simple rules to predict the influence of training dose have been ascertained.