These studies determined whether endogenous γ-aminobutyric acid (GABA) secretion affects LHRH neuronal responsiveness to norepinephrine (NE). The intracerebroventricular (icv) infusion of either bicuculline or phaclofen (GABAA or GABA-B receptor antagonists, respectively) into ovariectomized (OVX) estrogen-treated rats did not affect basal LH levels (95 ± 8.5 ng/ml) obtained over the 120 min of this study. When NE was infused icv, it produced a modest rise in plasma LH, which peaked within 15 min (240 ± 25 ng/ml) and then declined toward baseline over the next 90 min. In contrast, if bicuculline was given icv at about time zero, and NE was infused (icv) 15 min later, plasma LH secretion was markedly increased and reached a peak concentration of 723 ± 98 ng/ml within 15 min after NE treatment. Similarly, when bicuculline was infused into the medial preoptic area (MPOA), and NE was given 15 min later (icv), a peak LH level of 726 ± 105 ng/ml was obtained within 15 min.If phaclofen was given icv at about time zero, and NE was infused 15 min later, LH rose dramatically to reach a peak concentration of 844 ± 126 ng/ml within 15 min; a similar amplified LH response occurred when the GABA-B antagonist was infused into the MPOA and icv NE was given 15 min later. Comparisons of the LH responses obtained over the 120 min of the study suggest that icv infusions of the GABA-B receptor antagonist were more effective in sustaining peak LH secretion than the GABA-A receptor antagonist.In other groups of rats, the MPOA was electrochemically stimulated (ECS), and the effects of icv NE alone or combined with GABA receptor antagonists were evaluated. MPOA ECS alone induced a significant rise in plasma LH, which peaked between 35-45 min and then declined to approach basal levels by 150 min. In a second group, the MPOA was ECS, and at 30 min NE was infused icv. Plasma LH levels in these rats remained significantly elevated for the next 30 min before beginning their decline. In other animals, the MPOA was stimulated, and 15 min later either bicuculline or phaclofen was infused icv. Neither drug affected the patterns or concentrations of LH obtained after MPOA ECS alone. However, when rats received MPOA ECS plus either icv bicuculline or phaclofen, and these treatments were followed 15 min later by icv infusions of NE, LH secretion patterns and levels were altered significantly. Pretreatment with bicuculline did not affect the peak LH concentrations observed after MPOA ECS plus NE, but these high peak LH secretion levels were maintained for the next 105 min of the study. In contrast, when phaclofen was given to rats receiving preliminary MPOA ECS plus NE, LH secretion was further amplified within 15 min above that obtained in the control groups, but these higher plasma LH levels did not differ from those obtained after only phaclofen plus NE, and they were maintained for only 30 min before they began their decline.These observations indicate that LHRH neurons, in their normal resting state (e.g. when plamsa LH levels are low in this animal model) are relatively unresponsive to NE, and this diminished responsiveness may be due to the endogenous secretion of GABA from local inhibitory interneurons located within the MPOA. Moreover, the amplified LH responses to NE after the blockade of either GABA-A or GABA-B receptors suggests that both classes of GABA receptors may be involved in the regulation of LHRH neuronal responsiveness to NE. © 1990 by The Endocrine Society.
