COCAINE, CORTICOSTERONE AND EMOTIONAL BEHAVIOR

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Cocaine is one of the most potent reinforcers known; both humans and animals will crave and expend much energy to acquire these drugs. However, one of the many negative consequences of repeated cocaine use in humans is the development of panic and anxiety following cocaine withdrawal. Thus, cocaine has pleasurable, reinforcing properties, as well as anxiety-inducing effects. Although dopamine is known to be an important mediator of cocaine, stress hormones, such as corticosteroids, are thought to play a critical but paradoxical role in both the reinforcing and anxiety-inducing effects of cocaine. The goal of this proposal is to investigate the role of corticosteroids in the long-lasting anxiolytic (pleasurable) and anxiogenic properties of cocaine in rats. A paradigm that measures both long-lasting anxiolytic and anxiogenic effects of prior repeated cocaine administration by a single behavioral response, the acoustic startle reflex, will be described. Depending on the experience, both pleasurable and fearful states can be measured by the acoustic startle response. Startle decreases in an environment where the rats have previously been positively reinforced, and conversely, is increased following fear conditioning. The paradigm will be used to test the hypothesis that corticosteroids are critical for both the anxiolytic and anxiogenic effects of repeated cocaine following withdrawal. Adrenalecomized rats will be given repeated administration of cocaine, and then following a withdrawal period, will be tested for increased in pleasure and fear by measuring amplitude of the startle reflex. Corticosterone will also be given in an attempt to reverse the effects of adrenalectomy. In addition, pharmacological inhibition of corticosterone production will also be evaluated. The results will indicate whether corticosteroids are necessary for both the pleasurable and anxiety-inducing effects of cocaine, or for only one of the effects. The study will have important implications for understanding the environmental and behavioral control over the pleasurable and anxiogenic properties of cocaine and whether stress hormones regulate both of these properties or regulate cocaine-related pleasure and anxiety differentially. The outcome of the experiments should have ramifications for understanding drug abuse and relapse, and development of treatment and prevention strategies.