GABAergic Regulation of Lordosis: Influence of Gonadal Hormones on Turnover of GABA and Interaction of GABA with 5-HT

Abstract

The role of GABAergic neurons in activating female sexual behavior and possible mechanisms for GABAergic effects on behavior were examined in female rats. First, effects of the ovarian hormones estrogen and progesterone (P), at doses which promote lordosis, on levels and turnover/activity of GABA, were examined in brain areas which regulate lordosis. Utilizing AOAA, an inhibitor of GABA degradation, the accumulation rate of GABA (turnover/activity) was assessed in ovariectomized (Ovx), Ovx + estrogen and Ovx + estrogen + P-treated rats. Estradiol increased GABA accumulation rates in the arcuate-median eminence and in the area dorsal to and surrounding the VMN (VMN-S). P administration following estrogen priming enhanced GABA turnover in the medial preoptic area (mPOA) and further increased turnover in the VMN-S while GABA turnover decreased in the dorsomedial nucleus. No effects of hormones were noted in the VMN itself or in the dorsal midbrain central gray. Reverse dialysis of the GABA_A antagonist bicuculline into the basomedial hypothalamus was associated with a time-dependent inhibition of lordosis and a 300% increase in 5-HT release in the basomedial hypothalamus as measured by in vivo dialysis. These results provide additional evidence that GABAergic neurons mediate the physiological regulation of female sexual behavior and suggest that such mediation may involve an interaction with 5-HT containing neurons.

Orphanin FQ in the mediobasal hypothalamus facilitates sexual receptivity through the deactivation of medial preoptic nucleus mu-opioid receptors

“…Like OFQ/N, GABA induces inhibitory K+ currents in ARH POMC neurons that are modulated by estradiol (Nguyen and Wagner, 2006). Further, 3V bicuculline treatments that block GABA A receptors inhibited lordosis (Luine et al, 1999), and progesterone increases GABA turnover in the VMH region indicating progesterone may enhance GABA activity (Luine et al, 1997; McCarthy et al, 1990). The estradiol-only and estradiol + progesterone facilitation of sexual receptivity using different neurotransmitter systems may reflect multiple reproductive mechanisms that are present but used at different reproductive stages in the rat to coordinate behavior with the luteinizing hormone surge and ovulation.…”

Sex differences in estrogenic regulation of neuronal activity in neonatal cultures of ventromedial nucleus of the hypothalamus

“…GABA plays an important role in VMN development (7), and GABAergic neurotransmission has been implicated in E's effects on several important functions, such as sexual differentiation during neural development (8) and lordosis behavior (9). E has been shown to affect many aspects of GABAergic transmission, including GABA turnover rate (10), GABA synthesis enzyme glutamic acid decarboxylase (GAD) mRNA, and protein levels in the hypothalamus (11).…”

Neuroendocrine Hormonal Conditions in Epilepsy

“…161 GABA has substantial, regionally specific, complex effects on sexual function in animal studies. 162 OCBZ is an analogue of CBZ, with a comparable anticonvulsant efficacy. It has the advantage of low incidence of allergic reaction and better tolerated than CBZ in combined therapy.…”