THE DISCRIMINATION OF ABUSED DRUG MIXTURES The main aim is to explore the value, for the study of drug abuse, of a recent advance in drug discrimination methodology. Existing, well-developed methods for studying the discriminative stimulus effects of drugs focus almost exclusively on single drugs, whereas the abuse of mixtures of more than one drug at a time is a widespread health problem. A supplementary aim is to clarify understanding of the effects of single drugs with multiple effects; such drugs may be discriminated on the basis of a stimulus complex consisting of two or more components and the work will clarify ways in which such compound, interoceptive stimuli are processed. The novel approach proposed is based on methods for examining discriminative stimulus effects of drug mixtures in rats. Some basic principles underlying discrimination of mixtures have been evaluated in recent experiments with mixtures of nicotine and a benzodiazepine. In the work proposed, the discriminative stimulus effects of three different, abused mixtures will be examined: (1) amphetamine plus pentobarbital; (2) caffeine plus phenylpropanolamine; (3) pentazocine plus tripelennamine. Different groups of rats will be trained to discriminate each mixture, using two-bar, operant conditioning techniques. The ratios of doses of constituent drugs in the main experiments will be based on results of studies where effects of altering the dose-ratio will be studied systematically. The project will determine whether the effects of each of the three mixtures are perceived as the sum of their components, or whether distinctive, novel stimuli are generated. Characteristics, including specificity, of discriminative stimuli based on the three mixtures will be evaluated in generalization tests with the constituent drugs, with pharmacologically similar drugs, and with unrelated compounds. Control data will be obtained from rats trained to discriminate each of the constituent drugs of the mixtures. The information gained will aid the making of decisions on availability of some of the drugs and will provide a sounder pharmacological basis for treating abuse of mixtures.
