Hypothalamic opioid receptors mediate the inhibitory actions of corticotropin-releasing hormone on luteinizing hormone release: further evidence from a morphine-tolerant animal model

Recent experiments have shown that corticotropin-releasing hormone (CRH) inhibits gonadotropin hormone-releasing hormone (GnRH) and luteinizing hormone (LH) release, and endogenous opioid peptides have been implicated in the mediation of these effects. To further test this hypothesis, the effects of CRH on LH secretion was tested in rats that were made tolerant to the alkaloid opiate agonist morphine. Male rats were gonadectomized and 5 days later implanted with 2 pellets containing 75 mg of morphine each, for 48 h and with a third morphine pellet for the following 24 h. Rats were killed on the 4th day and their serum levels of LH were found to be similar to those of placebo-treated controls, indicating that the neural systems controlling LH secretion had become tolerant to the chronic exposure to morphine. The tolerant condition was confirmed in a subgroup of morphine-treated rats since an acute injection of morphine (5 or 10 mg/kg) did not further suppress LH levels in the chronically morphinized rats. The LH-suppressive efficacy of CRH (0.2 nmol, i.c.v.) was found to be markedly reduced in these morphine-tolerant rats compared to the opiate-naive animals. This finding thus further supports the view that opioid receptors partially mediate the inhibitory actions of CRH upon the GnRH-LH system.