EFFECTS OF GAMMA-AMINOBUTYRIC ACID-A RECEPTOR ANTAGONIST, BICUCULLINE, ON THE ELECTRICAL-ACTIVITY OF LUTEINIZING-HORMONE-RELEASING HORMONE PULSE-GENERATOR IN THE OVARIECTOMIZED RAT

The role of GABA neurons in the control of pulsatile release of LHRH w as investigated by checking the effect of the GABA(A) receptor agonist , muscimol, and antagonist, bicuculline, on the electrical activity of the luteinizing hormone-releasing hormone (LHRH) pulse generator in t he ovariectomized rat fitted with chronically implanted electrode arra ys in the medial basal hypothalamus. In untreated control animals, the hypothalamic multiunit activity (MUA) exhibited, at an average of 20. 5-min intervals, characteristic increases (volleys), each of which was associated with the initiation of an LH pulse. A bolus i.v. injection of muscimol (2 mg/kg) significantly increased the interval between MU A volleys and LH pulses without affecting the pulse amplitude. Continu ous i.v. infusion of saline increased the interval between MUA volleys to an average of 24.1 min without affecting the LH pulse amplitudes. Bicuculline infusion (10 mg/kg/h) altered neither the interval between MUA volleys nor the pulsatile release of LH. This was further checked in the condition where presynaptic inhibition by opioid peptides on t he noradrenergic system was presumably decreased by naloxone. Naloxone infusion (0.5 or 0.7 mg/kg/h) caused the MUA volleys to occur markedl y frequently, an average of 13.8-min intervals. The interval during co mbined infusion of bicuculline with naloxone was an average of 16.2 mi n, suggesting that bicuculline could not decrease the interval that wa s set by naloxone. The results show that, although exogenous GABA(A) r eceptor agonist is capable of inhibiting the activity of LHRH pulse ge nerator, the reduction in the endogenous GABA(A) receptor activity doe s not cause a significant effect, suggesting a minor role of inhibitor y GABA neurons in the control of pulsatile release of LHRH. Further, t ogether with the well-known fact that activation of GABA(A) receptor h yperpolarizes neurons postsynaptically, it is assumed that the GABAerg ic system, unlike the opioidergic one, is not involved in the presynap tic inhibition of the adrenergic receptor system which is probably imp licated in the frequency control of LHRH pulse generator.