Cortical involvement in cocaine sensitization

Cocaine challenge following chronic treatment produces enhanced behavioral responses compared to acute challenge in rats. We have shown that immediate early gene expression is similarly enhanced in neurons of the infralimbic cortex. In order to determine whether cocaine challenge affects nucleus accumbens {NAc) afferent circuits, fluorogold (FG) was injected into the NAc shell prior to chronic cocaine (10 mg/kg daily i.p. for 14 days) or saline vehicle treatment. After 7 days withdrawal, saline or cocaine challenge (30 mg/kg) was administered. Brains were removed I hr later and tissues were processed for in situ hybridization histochemistry to examine zif268 mRNA expression as an indicator of physiological activity. FGlabeled neurons were present in the infralimbic cortex, basolateral amygdala, ventral hippocampus, subiculum and other regions, but zif268 mRNA expression was only induced compared to acute treatment in FG-Iabeled neurons located in the infralimbic cortex. Amygdalar neurons exhibited similar levels of labeling across all groups, however, zif268 mRNA expression was induced in a greater number of amygdalar neurons thai innervate the NAc shell during cocaine withdrawal. Neither the number of hippocampal neurons that innervate the NAc shell nor the amount of zif268 labeling in these neurons was altered. These data suggest that enhanced activity of glutamatergic neurons in the infralimbic cortex as well as recruitment of additional amygdalar neurons that innervate the NAc shell might underlie sensitized behavioral responses related to NAc activity.