Naloxone antagonism of corticotropin-releasing hormone stimulation of prolactin secretion in rhesus monkeys.

The effect of opiate receptor blockade on human CRH-induced PRL secretion was examined in ovariectomized and normal female rhesus monkeys. A bolus iv dose of 100 micrograms CRH acutely stimulated PRL secretion in both normal and ovariectomized animals. The magnitude of the PRL response was greater in ovariectomized monkeys (212% increase; n = 5) than in normal monkeys (56% increase; n = 5). Naloxone pretreatment inhibited CRH-induced PRL release in a dose-dependent fashion, whereas nalmefene did not, in both normal and ovariectomized monkeys. Administration of nalmefene alone significantly stimulated PRL secretion in normal monkeys (57% increase; n = 10), but not in ovariectomized monkeys (10% increase; n = 10). Naloxone alone had no effect. Since nalmefene has a high affinity for both the kappa- and mu-receptors whereas naloxone binds primarily to the mu-receptor, these results suggest that CRH-induced PRL secretion in monkeys is mediated by an endogenous opiate which binds to an opiate receptor other than or in addition to the mu- and kappa-receptors.