There is growing interest in the possibility that drugs of abuse subvert normal learning and decision- making processes, leading to the development of compulsive, pathological drug-seeking behavior. Chronic exposure to psychostimulants, like cocaine, results in sensitization of nigrostriatal and mesolimbic dopamine pathways, which are critically involved in the acquisition of habits (i.e., rigid, stimulus-bound responses) and the expression of incentive motivation (i.e., the capacity for a reward-related cue to facilitate appetitive behaviors, or induce 'wanting'). In this project, we will evaluate two distinct (but not mutually exclusive) theories of addiction: that drug exposure allows habits to dominate the control of action selection (at the expense of deliberative, goal-directed action selection), and that drug exposure potentiates the influence of reward-related environmental cues over performance. Our plan is to use a combination of carefully controlled behavioral procedures and well-established neurochemical detection techniques to answer the following questions: (i) Does dopamine release during instrumental training match the profile of the prediction error-based reinforcement signal assumed to be responsible for governing habit formation? (ii) What are the effects of cocaine pre-exposure on the acquisition and expression of habitual performance and on reinforcement-related dopamine signaling? (iii) Does mesolimbic dopamine efflux mediate the incentive motivational processes that guide cue-based action selection? (iv) and, What are the effects of repeated cocaine exposure on cue-based action selection and on the mesolimbic dopamine response to reward-related cues? Recent studies have shown that response-contingent cocaine elicits stronger neurochemical effects and results in more dramatic and longer-lasting changes in the circuitry underlying dopamine release than noncontingent cocaine. Such findings raise questions about the validity of studies assessing the effects of experimenter-administered drugs on learning, behavioral control, and brain chemistry. Therefore, a secondary objective of the current application is to determine whether the behavioral and neurochemical effects of repeated cocaine exposure depend on the mode of drug delivery.

Public Health Relevance

Repeated exposure to drugs of abuse, including psychostimulants like cocaine, can significantly alter the neurocircuitry that supports learning and decision-making. Modern theories of addiction propose that these alterations lead to the compulsive, pathological drug-seeking behavior displayed by addicts. The current application combines well-established behavioral tests with neurochemical analysis to investigate how taking cocaine influences the way organisms acquire and select actions.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
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Lynch, Minda
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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