The effects of adrenalectomy were investigated on the binding properties of [ (3)H] N- propylnorapomorphine ([(3)H]NPA) binding sites in membrane preparations from the rat neostriatum. Adrenalectomy (1 week) was found to increase the K(D) value of [(3)H]NPA binding sites by 30 +/- 3%, without affecting the B(max) values. These effects were fully counteracted by replacement treatment with corticosterone (5 mg/kg, twice daily, 1 week, last injection given 2 h before killing). The ability of neurotensin and cholecystokinin-8 (sulphated) in vitro to increase the K(D) value of [(3)H]NPA binding sites was maintained also following adrenalectomy. The average increases were 16+/-7 and 21+/-6%, respectively. When added together the two peptides failed to increase the K(D) value any further. The B(max) values of [(3)H]NPA binding sites were not affected by either adrenalectomy or by the peptides. These results indicate a glucocorticoid regulation of the binding characteristics of dopamine D-2 receptors in the rat striatum. The mechanism mediating the effects of adrenalectomy may involve an altered expression or regulation of the D-2 receptor or of its connected G-proteins. Probably, it is different from the mechanism whereby the neuropeptides modulate the D-2 receptor, since the neuropeptide-induced modulation was also maintained following the changes induced by adrenalectomy.