This proposal studies the behavioral pharmacology of oral cocaine self-administration. The optimal conditions for the induction of cocaine overindulgence in rats will be established by varying drug concentration and the food-schedule induction parameters which are known to produce excessive behaviors. The effect commonly- used and abuse licit agents (nicotine and caffeine) might have in increasing schedule-induced cocaine intake will be determined, as well as possible attenuating effects of promising therapeutic (desipramine) and blocking agents (e.g., chlorpromazine and pimozide). A number of commodities and activities will be tested as behavioral alternatives to available cocaine under the excessive-behavior-generating conditions. Extensive exposure to prior experiences with non-drug, highly-preferred substances such as saccharin (which are then made unavailable) under conditions that should induce cocaine abuse may block its development, as may pre-adaptation to the inducing conditions. The possibility that prior overindulgence of nicotine or caffeine may predispose to cocaine abuse development will be explored. The effect of parenteral cocaine injection on a fine motor control task will be determined, as well as the interactive effects of caffeine and of nicotine with chronic cocaine on this kind of performance. Serum cocaine and metabolite levels will be correlated with behavioral effects.
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