Glucocorticoids and behavioral effects of psychostimulants. I: locomotor response to cocaine depends on basal levels of glucocorticoids.

In this study, we explored the influence of corticosterone, the major glucocorticoid in the rat, on the locomotor response to cocaine. In particular, in a first series of experiments, we determined the effects of suppressing endogenous glucocorticoids by adrenalectomy on a full dose-response curve of cocaine-induced locomotion and the influence, on this behavioral response, of different corticosterone concentrations, by implanting different corticosterone pellets in adrenalectomized rats. Adrenalectomy decreased the locomotor response to cocaine, inducing a vertical shift in the dose-response curve, and corticosterone dose-dependently reversed the decrease induced by adrenalectomy. The effects of adrenalectomy were fully replicated by the acute central infusion of corticosteroid receptor antagonists, and the action of glucocorticoids did not seem to depend on nonspecific effects such as a general alteration of motor responses or drug metabolism. Thus, neither adrenalectomy, corticosterone receptor antagonists nor corticosterone replacement modified saline-induced locomotion and the administration of corticosterone did not increase locomotion. Furthermore, adrenalectomy slightly increased brain concentrations of cocaine, an effect that cannot account for the decrease in drug-induced locomotion it induced. In a second series of experiments, we tested whether corticosterone levels at the time of adrenalectomy could influence the outcome of this surgical procedure on the locomotor response to cocaine. We thus adrenalectomized rats under different conditions resulting in different levels of the hormone. Corticosterone levels at the moment of adrenalectomy had dose-dependent long-term facilitatory effects on the response to the drug. These findings underline a facilitatory role of glucocorticoids in the behavioral effects of psychostimulant drugs.