Injection of bicuculline elicits firing of luteinizing hormone releasing hormone pulse generator in muscimol-treated ovariectomized rats

Abstract

We have already demonstrated that, although exogenous γ-aminobutyric acid A (GABA A) receptor agonist is capable of inhibiting the activity of luteinizing hormone releasing hormone (LHRH) pulse generator, the reduction in the endogenous GABA A receptor activity does not have a significant effect in ovariectomized rats, suggesting a minor role of inhibitory GABA neurons in the control of pulsatile release of LHRH. In this study, we further analyzed the role of the GABA A receptor system in the regulation of LHRH pulse generator activity observed by recording the multiunit activity (MUA) in the hypothalamus of ovariectomized rats. An abrupt increase (volley) in the MUA in the arcuate nucleus (ARC)-median eminence region (ME) was accompanied by the initiation of a luteinizing hormone (LH) pulse, determined by measuring LH concentrations in blood sampled simultaneously. The injection of 1–3 mg/kg muscimol (MUS), a GABA A receptor agonist, decreased the basal MUA and delayed the occurrence of the next MUA volley, but it did not change the LH pulse amplitude. I.v. injection of 5 mg/kg bicuculline (BIC), a GABA A receptor antagonist, during continuous infusion of MUA (5 mg/kg/h) which decreased the basal MUA and prevented the MUA volley from occurring, evoked MUA volleys and LH pulses whose amplitudes were similar to those found before the MUS infusion. Injection of the same dose of BIC during the infusion of saline increased the MUA transiently, but this increase was not accompanied by an LH pulse and afterwards there occurred MUA volleys at ordinary intervals accompanied by LH pulses with unchanged pulse amplitudes. These results suggest that the GABA A receptor activity nhibits the LHRH pulse generator activity and that when the GABAergic activity is extremely high, a reduction in the GABA A receptor activity is able to cause activation of the LHRH pulse generator in the ovariectomized condition.