DOPAMINE-DEPENDENT RESPONSES TO MORPHINE DEPEND ON GLUCOCORTICOID RECEPTORS

Previous work has shown that glucocorticoid hormones facilitate the be havioral and dopaminergic effects of morphine. In this study we examin ed the possible role in these effects of the two central corticosteroi d receptor types: mineralocorticoid receptor (BIR), and glucocorticoid receptor (GR), To accomplish this, specific antagonists of these rece ptors were infused intracerebroventricularly and 2 hr later,ve measure d: (i) locomotor activity induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity induced by an infusion of morphine (1 mu g per side) into the ventral tegmental area, which is a dopamine -dependent behavioral response to morphine; (iii) morphine-induced dop amine release in the nucleus accumbens, a dopaminergic projection site mediating the locomotor and reinforcing effects of drugs of abuse. Bl ockade of MRs by spironolactone had no significant effects on locomoti on induced by systemic morphine. In contrast, blockade of GRs by eithe r RU38486 or RU39305, which is devoid of antiprogesterone effects, red uced the locomotor response to morphine, and this effect was dose depe ndent. GR antagonists also reduced the locomotor response to intravent ral tegmental area morphine as well as the basal and morphine-induced increase in accumbens dopamine, as measured by microdialysis in freely moving rats, In contrast, spironolactone did not modify dopamine rele ase. In conclusion, glucocorticoids, via GRs, facilitate the dopamine- dependent behavioral effects of morphine, probably by facilitating dop amine release. The possibility of decreasing the behavioral and dopami nergic effects of opioids by an acute administration of GR antagonists may open new therapeutic strategies for treatment of drug addiction.