Recent research has shown that prazosin, a drug developed for its cardiovascular actions (presumably through interactions with alpha1 adrenoceptors), can completely reverse some behavioral effects of cocaine. Preliminary research in our laboratory has revealed that this antagonism is not consistently observed, even under conditions that are very similar to those reported in the literature. Our preliminary work has also revealed that manipulation of motivational variables can alter the nature of the cocaine-prazosin interaction. We propose, therefore, to examine more thoroughly the way in which motivational variables and other variables known to influence strength of """"""""purposive"""""""" responding modulate the interaction of prazosin with cocaine. Specifically, we propose to study operantly conditioned behavior of pigeons and squirrel monkeys since operant performance in these two species has been used to demonstrate antagonism of cocaine's effects by prazosin. First, effects of level of food deprivation, of amount of reinforcement, and of amount of responding required for reinforcement will be studied in pigeons. Subsequently, species generality of major findings will be determined by studying squirrel monkeys, and the context specificity of prazosin's ability to antagonize cocaine will be examined. Later research will focus on an analysis of the crucial behavioral factors that determine whether prazosin will block effects of cocaine and may also be directed at examining behavioral modification of antagonistic actions of other drugs. Identification and characterization of drugs that will block effects of cocaine have obvious relevance to the prevention and treatment of cocaine addiction and abuse.
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