The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent

The dopaminergic projection to the shell of the nucleus accumbens is the mo st reactive to stress, reward and drugs of abuse and this subregion of the nucleus accumbens is also considered a target of therapeutic effects of aty pical antipsychotic drugs (APD). In this report we show, by means of in viv o microdialysis and Fos immunohistochemistry, that the hyper-responsiveness which characterizes the dopaminergic transmission to the shell is dependen t on glucocorticoid hormones. In Sprague-Dawley rats, after suppression of endogenous glucocorticoids by adrenalectomy, extracellular dopamine levels selectively decreased in the shell, whilst they remained unchanged in the c ore. This effect was observed in basal conditions, after a mild stress (veh icle injection), as well as after subcutaneous administration of morphine ( 2 mg/kg, s.c.) or intraperitoneal injection of cocaine (15 mg/kg, i.p.). Th e decrease in dopamine observed in the shell had a postsynaptic impact, as shown by less induction of Fos-like proteins selectively in the shell in re sponse to cocaine. However, the induction of Fos-like proteins by the full D-1 agonist SKF82958 (1.5 mg/kg, i.p.) remained unchanged after adrenalecto my, suggesting that the changes in Fos expression after cocaine injection w ere likely to depend on changes in extracellular dopamine levels rather tha n on changes in postsynaptic sensitivity to dopamine. The effects of adrena lectomy were glucocorticoid-specific given that they were prevented by cort icosterone treatment. This anatomical specificity in the control of neurona l activity by a hormonal input highlights the role of steroid hormones in s haping the functional activity of the brain.