The main aim is to explore the characteristics of behavior based on the discriminative stimulus effects of drug mixtures. Existing, well-developed methods for studying discriminate stimulus effects on 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 secondary aim is to clarify understanding of the effect of single drugs with multiple effects; such drugs may be discriminated as a stimulus complex consisting of two or more elements and studies will clarify ways in which such a compound, interoceptive stimuli are processed. In the work proposed, the effects of behavioral and pharmacological variables on the characteristics of discriminations based on drug mixtures will be examined in greater depth than was the case previously. All experiments will utilize two-bar, operant conditioning procedures in rats and in some cases novel forms of these methods will be evaluated. While including comparisons of the discriminative effects of abused mixtures of amphetamine plus pentobarbital with those of non-abused mixtures of nicotine plus midazolam, the project will determine the influence of different training procedures and of different previous behavioural and pharmacological histories. Behavioural mechanisms that may account for some interactions between drugs in mixtures will be examined, based upon effects that associative learning theorists call blocking and overshadowing. The effects of antagonists, and the roles of the doses and dose-ratios of drugs used for training will be determined. The specificity of discriminative stimuli trained in different ways will be evaluated in generalization tests with pharmacologically similar drugs and drug mixtures, and with compounds from other pharmacological classes. The work will suggest ways in which environmental factors may modify responses to drug mixtures and thus influence the individual potential for engaging in addictive behaviors.
