DIFFERENTIAL REGULATION OF LUTEINIZING-HORMONE RELEASE BY GAMMA-AMINOBUTYRIC-ACID RECEPTOR SUBTYPES IN THE ARCUATE-VENTROMEDIAL REGION OF THE CASTRATED RAM

We investigated the effects on LH secretion of infusing gamma-aminobut yric acid (GABA) agonists muscimol and baclofen (GABA(A) and GABA(B) r eceptor agonists, respectively) into either the medlar preoptic area ( mPOA) or the arcuate-ventromedial region (ARC-VMR) of the hypothalamus of castrated rams during the nonbreeding season. Bilateral microdialy sis of artificial cerebrospinal fluid for 4 h followed by treatment wi th artificial cerebrospinal fluid, baclofen (1 mM), or muscimol (1 mM in the ARC-VMR, 250 mu M in the mPOA) for 4 h was carried out on three separate occasions in random order. Simultaneously, jugular venous bl ood was collected at 10-min intervals, and plasma later was assayed fo r LH. The estimated dose of baclofen delivered to each unilateral micr odialysis site was 7.9 mu g; for muscimol, it was 1.1 mu g for the mPO A and 4.5 mu g for the ARC-VMR. In the mPOA, baclofen had no detectabl e effect, whereas muscimol had a delayed suppressive effect on mean LH (P < 0.01). In the ARC-VMR muscimol rapidly reduced mean LH (P < 0.01 ). In contrast, baclofen increased mean LH (P = 0.01) and LH pulse amp litude (P = 0.05) without altering the LH interpulse interval (P > 0.1 0). These results support the involvement of GABA(A) receptors in the mPOA in regulating LH secretory patterns. More importantly, both GABA( A) and GABA(B) receptors in the ARC-VMR appear to differentially modul ate LH and, presumably, GnRH release. Whether GABA acts directly on th e GnRH neuron or indirectly through other neural systems remains to be determined.