? Stress is believed to play a critical role in the vulnerability and relapse to addiction. Behavioral sensitization to psychostimulant drugs is an enduring form of neural plasticity in limbic brain regions clearly implicated in addiction, and is defined as an increase in drug effect with repeated drug or stress exposure. Previous studies suggest that an intact hypothalamic-pituitary-adrenal axis is important for the development of drug- and stress-induced sensitization, but little is known about the molecular and anatomical targets at which adrenal stress hormones act to mediate this process. The medial prefrontal cortex contains high levels of glucocorticoid receptors and lesions of this area disrupt drug-induced sensitization, suggesting a role for glucocorticoid receptors of this region in behavioral sensitization. In this application, I hypothesize that activation of glucocorticoid receptors in the medial prefrontal cortex contributes to the development of behavioral sensitization. The goals of this proposal are to: 1) elucidate the role of medial prefrontal cortex glucocorticoid receptors in drug- and stress-induced sensitization through antagonist studies and 2) determine if glucocorticoid receptor activation in the medial prefrontal cortex will facilitate the development of sensitization to psychostimulant drugs. ? ? ? ?
