The aims are to explore behavioral effects of some abused drug mixtures, to use recently developed methods to analyze discriminative effects of single drugs with multiple effects, and to explore the potential of Occasion Setting in relation to drug action. Both mixtures of drugs and single substances with multiple effects will be analyzed as compound interoceptive stimuli, bringing to drug action the theoretical framework of associative learning that is more commonly used in studies of compound exteroceptive stimuli. The emphasis will be upon mixtures of which one component is an opioid, notably mixtures of heroin plus cocaine (""""""""speedballs"""""""") and of pentazocine plus tripelennamine (""""""""T's & blues""""""""). Experiments will use methods developed previously in the project: [1] the AND-discrimination procedure will provide sensitive measures for detecting interactions between drugs in mixtures and [2] the AND-OR discrimination procedure will be used to enhance the pharmacological specificity of stimuli produced by mixtures. The first experiments on Occasion Setting with drugs in two-lever paradigms will be carried out. The specificity of discriminative stimuli produced by mixtures of abused substances such as heroin plus cocaine will be evaluated in tests with pharmacologically similar drugs and drug mixtures, and with compounds from other pharmacological classes. Similarities and differences between different abused and non-abused mixtures will be determined to identify the key drug actions responsible for the characteristic effects of the mixtures. These techniques will be used to analyze in greater depth than previously the discriminative effects of single opioid drugs with multiple effects; the mixed agonist-antagonist opioids cyclazocine, pentazocine, buprenorphine and butorphanol may produce their characteristic effects and patterns of abuse through different profiles of effects across m- and k-opioid, NMDA and s receptors. Cyclazocine will be a reference drug and experiments with it will be primarily to standardize methods; the other mixed agonist-antagonists have different, less well-understood effects and neuropharmacological actions, but are of greater present-day clinical significance. Profiles of effects of these drugs will be examined for their intrinsic importance and to inform studies on their actions in mixtures with tripelennamine and cocaine.
