GLUTAMATE AND CRAVING FOR COCAINE

Medical University Of South Carolina, Charleston SC

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Abstract

Addiction to cocaine results in a number of long-term behavioral changes. Particularly insidious is the development of craving for the drug during abstinence. Craving is a primary cause of relapse, and to date little information is available on the neural substrates that mediate the behavioral expression of craving. This research proposal attempts to address this lacuna in our understanding. It is hypothesized that the repeated exposure to cocaine progressively augments the activity of corticofugal glutamatergic efferents to the nucleus accumbens, and that this excitatory input initiate both drug- and environmentally-induced craving for cocaine. To test this hypothesis, rats will be trained to self- administered intravenous cocaine. Once stable levels of self- administration are achieved, the behavior will be extinguished and aspects of the neural basis of the reinstatement of cocaine-seeking behavior will be examined.. Reinstatement will be induced by 1) the microinjection of glutamatergic drugs into the nucleus accumbens, 2) systemic cocaine in rats pretreated with drugs into the nucleus accumbens, 3) the presentation of conditioned cues after pretreatment with glutamatergic drugs, and electrical stimulation drugs, and 4) electrical stimulation of cortical regions providing glutamatergic afferents to the nucleus accumbens. In addition, microdialysis will be employed to estimate changes in glutamate transmission in the nucleus accumbens following cocaine or cue-induced reinstatement.