THE ROLE OF ENDOGENOUS OPIOIDS IN THE LUTEINIZING-HORMONE SURGE IN RATS - STUDIES WITH CLOCINNAMOX, A LONG-LASTING OPIOID RECEPTOR ANTAGONIST

Endogenous opioid peptides have been demonstrated to regulate luteiniz ing hormone (LH) secretion in a variety of species. Studies in rodents suggest a role of opioid peptide systems in controlling the timing of the LH surge, which is entrained to the circadian rhythm. The current studies utilize clocinnamox, a novel long-lasting opioid receptor ant agonist that is capable of occupying mu-opioid receptors for periods o f one week or more, to examine the role of endogenous opioid systems o n the LH surge. Administration of clocinnamox lorocinamoylamino)-7,8-d ihydro-N-cyclopropylmethyl normophineone mesylate]) on the morning of proestrus advanced the LH surge by several hours. Despite the blockade of opioid receptors and analgesia for more than one week, administrat ion of clocinnamox on the evening of diestrus II had no effect on the timing of the LH surge bur significantly increased plasma LH levels th roughout the day of proestrus. These data suggest that removal of opio id tone is unlikely to be the critical signal controlling the initiati on of the LH surge in rodents, although it does appear to be permissiv e for the surge. Furthermore, the mu-opioid receptor appears to be the receptor involved in the regulation of the LH surge. (C) 1998 Elsevie r Science B.V. All rights reserved.