The goal of this proposal is to delineate the brain regions and determine the role and location of non-NMDA receptors activated by cocaine-related stimuli. Evidence suggests that limbic regions, and in particular, the nucleus accumbens is involved in the expression of conditioned responses to psychomotor stimulant drug cues. Recent evidence suggests important roles for both NMDA and non-NMDA receptor mechanisms. NMDA receptors have been implicated in the development of associations between cocaine and stimuli repeatedly paired with cocaine. Of more clinical significance are findings implicating non-NMDA receptors in the expression of the behavioral responses to cocaine-related stimuli. The studies proposed here will test the hypothesis that non-NMDA receptor mechanisms participate in cocaine-induced conditioned hyperactivity. A non-NMDA receptor antagonist will be infused into brain regions previously identified as being activated by conditioning using Fos immunohistochemistry. The ultimate goal of the PI is to show that novel pharmacotherapies may be developed for the treatment of conditioned cravings in individuals addicted to cocaine.
