GLUCOCORTICOIDS AND BEHAVIORAL-EFFECTS OF PSYCHOSTIMULANTS .1. 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 pa rticular, in a first series of experiments, we determined the effects of suppressing endogenous glucocorticoids by adrenalectomy on a full d ose-response curve of cocaine-induced locomotion and the influence, on this behavioral response, of different corticosterone concentrations, by implanting different corticosterone pellets in adrenalectomized ra ts. adrenalectomy decreased the locomotor response to cocaine, inducin g a vertical shift in the dose-response curve, and corticosterone dose -dependently reversed the decrease induced by adrenalectomy. The effec ts of adrenalectomy were fury replicated by the acute central infusion of corticosteroid receptor antagonists, and the action of glucocortic oids did not seem to depend on nonspecific effects such as a general a lteration of motor responses or drug metabolism. Thus, neither adrenal ectomy, corticosterone receptor antagonists nor corticosterone replace ment modified saline-induced locomotion and the administration of cort icosterone did not increase locomotian. Furthermore, adrenalectomy sli ghtly 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 surgi cal procedure on the locomotor response to cocaine. We thus adrenalect omized rats under different conditions resulting in different levels o f the hormone. Corticosterone levels at the moment of adrenalectomy ha d 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.