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The Journal of Neuroscience, September 15, 2000, 20(18):7109-7115

Acute and Chronic Dopamine Dynamics in a Nonhuman Primate Model of Recreational Cocaine Use

Charles W. Bradberry

Departments of Psychiatry and Laboratory Medicine, West Haven Veterans Administration Hospital and Yale University School of Medicine, West Haven, Connecticut 06516

Using a model of recreational cocaine consumption, we have determined in four rhesus monkeys the impact of self-administered cocaine on mesolimbic and sensorimotor striatal dopaminergic neurotransmission. The effects of cocaine repeated within a self-administration session and across multiple sessions over a 6 month period were determined by the use of fixed-ratio self-administration and microdialysis procedures. The exposure to cocaine was modest, with at most two 0.5 mg/kg infusions permitted in each weekly session. Within a cocaine self-administration session, acute tolerance to the ability of cocaine to elevate extracellular striatal dopamine was observed. Over a period of 6 months of repeated self-administration, there was a significant increase in the impact of a fixed dose on extracellular dopamine, indicating that neurochemical sensitization to the effects of self-administered cocaine occurs in primates. A pronounced dopaminergic response to noncontingent cocaine was also observed, with no increases in extracellular dopamine in response to an unexpected saline substitution, indicating that the neurochemical response to self-administered cocaine is primarily caused by direct pharmacological effects of the drug rather than by conditioning to external environmental cues. These results highlight the contrast in time-dependent changes in neurochemical responsiveness to cocaine, depending on whether within-session or between-session comparisons are made. They also demonstrate that recreational levels of cocaine consumption can result in neurochemical sensitization, an enduring change in brain function that may contribute to addiction.

Key words: dependence; striatum; reward; relapse; psychostimulant; accumbens

Copyright © 2000 Society for Neuroscience  0270-6474/00/20187109-07$05.00/0


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