Opiate-serotonin synergism stimulating luteinizing hormone release in estrogen-progesterone-primed ovariectomized rats: mediation by serotonin2 receptors.

A tonic inhibition of LH release by endogenous opiate systems is apparent after administration of opiate antagonists to ovariectomized estrogen-progesterone-primed rats. In the presence of a serotonin agonist, morphine has been found to stimulate LH release in ovariectomized animals. Thus, in the present study the individual effects as well as interactions of the opiate and serotonin (5HT) systems have been examined using morphine and quipazine, respectively, as agonists and ketanserin (5HT2) and methysergide (5HT1 and 5HT2) as antagonists. Rats ovariectomized 2-4 weeks beforehand were primed with estradiol benzoate (15 micrograms; day 0) and progesterone (5 mg; day 2). Serial blood samples were collected from unrestrained rats via a jugular cannula inserted 3 days before, and plasma LH was measured by RIA. Neither morphine (4 mg sulfate) nor quipazine (2 mg/kg) administered iv at 1200 h significantly elevated plasma LH at 1210, 1220, or 1230 h compared to levels at 1200 h, although plasma LH concentrations at these times were significantly greater than those in animals receiving saline at 1200 h. However, injection of both morphine and quipazine at 1200 h greatly augmented LH release at 1210, 1220, and 1230 h compared to the response to either drug alone. The duration of the significant elevation of plasma LH was limited to 10 min by ketanserin (2.5 mg/kg, ip, at 0900 h) and to 20 min by methysergide (10 mg/kg, ip, at 0900 h), suggesting mediation of this response by 5HT2 receptors. These results suggest the possibility of an important interaction between opiate and serotonergic systems in controlling the release of LH and raise the intriguing question of its role, if any, in controlling events of the estrous cycle.