Cocaine addiction in North America is a medical problem with profound social and financial cost. Approximately 2 million Americans use cocaine habitually, and those seeking treatment find it extraordinarily difficult to abstain and relapse rates are high. A medication that would help control the cravings for cocaine during the early stages of therapy would help retain patients in treatment programs. An animal model is essential for testing potentially therapeutic drugs and for evaluating the underlying neurobiology of drug abuse. This proposal will address two key features of the addictive process. The first is a progressive increase in the motivation to take cocaine and the second is the emergence of binge patterns of drug use. Cocaine self-administration in rats will be used to model these fundamental aspects of human drug taking. A novel procedure has been developed that permits continual access to cocaine (during discrete trials) throughout the 24 dark/light cycle. Different patterns of intake (either circadian or binge-like) are engendered depending on the dose and frequency of the trials. The overall objective of this proposal is to define the critical factors that model the addictive process. Specifically we will (1) define the parameters that affect the transition from controlled (circadian) intake to binge-like, dysregulated patterns of self-administration, (2) identify factors that lead to motivational changes across the cocaine addiction process (such as total intake, pattern to intake, and drug-free periods) and (3) characterize individual differences in the development of binge-like patterns of intake and an increased motivation to self-administer cocaine.
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