Effects of naloxone on basal and stress-induced ACTH and corticosterone secretion in the male rat--site and mechanism of action.

The acute effects of naloxone upon basal and stress-induced secretion of ACTH and corticosterone (CS) in the adult male rat were investigated. Forty-five minutes subsequent to naloxone injection (5 mg/kg body wt, i.p.), basal serum levels of ACTH (by radioimmunoassay) and of CS (by corticosterone-binding globulin) were more than doubled, as compared to vehicle-treated animals. Upon exposure to either photic or audiogenic stress, the ACTH and CS secretory responses were greater in the naloxone-injected groups. In animals with complete hypothalamic deafferentation basal serum ACTH concentrations were significantly greater than in intact controls (2-fold), and naloxone elicited a further doubling of this parameter. In dexamethasone-pretreated rats (50 micrograms/animal, 4 h prior to naloxone), naloxone had no effect upon ACTH and CS secretion. This study demonstrates: (1) that acute naloxone administration leads to hypersecretion of ACTH, as well as of CS, in the adult male rat; and (2) that its effect is due to an action within the hypothalamo-hypophyseal unit. The data also suggest that these naloxone effects are not mediated by glucocorticoid hormones.