Evidence that amplification of norepinephrine-induced LH release by morphine is indirectly due to suppression of tuberoinfundibular dopamine secretion

Abstract

We previously observed that morphine markedly amplifies LH secretion following intracerebroventricular (i.c.v.) norepinehrine (NE) infusions. Based on additional evidence, we hypothesized that perhaps these morphine effects were due to suppression of tuberoinfundibular dopamine (TIDA) secretion thus allowing NE to evoke a greater release of LHRH from axon terminals in the median eminence than would otherwise occur. In the present studies, we examined whether apomorphine (a DA receptor agonist) would suppress and haloperidol (a DA receptor antagonist) would mimic these enhancing effects of morphine on NE-induced LH secretion. Estrogen-treated ovariectomized rats were used in these studies. NE, when infused i.c.v. (45 μg) evoked a modest increase in plasma LH(1.1 ± 0.2to2.2 ± 0.2ng/ml) within 15 min. When morphine sulfate (10 mg/kc s.c.) was given 15 min prior to NE, LH peak values of11 ± 2ng/ml were obtained by 60 min. Treatment of rats with apomorphine (1.5 mg/kg s.c.) at −15 min, morphine at 0 min and i.c.v. NE at 15 min resulted in a significant blunting of morphine's effect on NE-induced LH release. Moreover, in all morphine-treated rats, plasma prolactin (PRL) increased significantly within 10 min, peaked at 30 min and declined towards basal values by 90 min. Apomorphine completely blocked this morphine effect of PRL release. Haloperidol (HAL; 2.5 mg/kg s.c.) treatment had no effect on basal LH release but resulted in a significant increase in PRL which remained elevated up to 180 min. When HAL was given at 0 min and NE was infused i.c.v. at 15 min, a rapid, progressive and highly significant temporal increase in LH secretion occurred with peak values of20.4 ± 4ng/ml being reached by 90 min. Since our other recent studies have shown that i.c.v. DA infusions neither amplify nor suppress NE-induced LH release nor do they affect basal LH levels when given alone, we could not attribute morphine's action on NE release to alterations in A15 or A14 DA neuronal activity nor to increases in hypothalamic incertohypothalamic (A13) DA secretion. Rather, the suppression of TIDA (A12) neuronal activity or blockade of DA receptors by morphine or HAL, respectively, suggest that amplification of NE-induced LH release may be due to the suppression of inhibitory DA influences on the release of LHRH from axon terminals within the median eminence. The implications of these opiate actions on preovulatory LH surges are discussed.