GAMMA-AMINOBUTYRIC ACID-OPIOID INTERACTIONS IN THE REGULATION OF GONADOTROPIN-SECRETION IN THE IMMATURE FEMALE RAT

Previous studies in the male rat have demonstrated that GABA acting via GABA(B) receptors can abolish naloxone-induced LH secretion. The purpose of the present study was to determine if an analogous situation exists in the female rat. Naloxone administered to ovariectomized immature rats had no effect on LH release. In contrast, naloxone potently stimulated LH release in estrogen-primed ovariectomized immature rats. Elevation of endogenous brain levels of GABA by administering amino-oxyacetic acid, an inhibitor of GABA catabolism, prevented the naloxone-stimulated release of LH. This effect appeared to be both GABA(A) and GABA(B) receptor mediated, since exogenous administration of either muscimol (GABA(A) agonist) or baclofen (GABA(B) agonist) prevented the naloxone-induced release of LH. Neither GABA agonist had any effect on LHRH-stimulated LH release in vivo, suggesting that their effect was specific and achieved at the level of the CNS. In contrast to its inhibitory effect on naloxone-stimulated LH and FSH release, muscimol increased basal LH and FSH release in vivo and from hemipituitaries incubated in vitro, while having no effect on LHRH release from mediobasal hypothalamic and preoptic area fragments in vitro. Thus, under conditions of basal LH release, activation of GABA(A) receptors in the anterior pituitary can actually lead to enhanced LH secretion. Finally, naloxone-stimulated LH release was found to be inhibited by the alpha1- and alpha2-adrenergic blockers, prazosin and yohimbine, suggesting that naloxone-stimulated LH release is mediated via catecholamine neurotransmission involving alpha1- and alpha2-adrenergic receptor activation. These studies provide insights into the complex effects of GABA on basal and elevated LH secretion in the female rat, and they demonstrate a sex difference in the ability of GABA(A) and GABA(B) receptor activation to modulate naloxone-stimulated LH secretion.