The GABAB Antagonist CGP 52432 Attenuates the Stimulatory Effect of the GABAB Agonist SKF 97541 on Luteinizing Hormone Secretion in the Male Sheep

Abstract

The objectives of this study were to determine if the c-aminobutyric acid (GABA)B agonist, 3-aminopropyl (methyl) phosphinic acid (SKF97541), would increase luteinizing hormone (LH) secretion when infused by microdialysis into the medial basal hypothalamus (MBH) of the castrated ram, and to determine if the action of SKF97541 would be attenuated by coinfusion of the GABAB antagonist CGP52432. Initial experiments established that infusion of SKF alone, at concentrations as low as 5 μM, increased mean LH, LH pulse amplitude, and in some cases, pulse interval. In the last experiment, animals were treated with artificial cerebrospinal fluid (CSF) alone, SKF alone (30 μM), 3-[[(3, 4-dichlorophenol) methyl] amino] propyl] dieth-oxymethyl) phosphinic acid (CGP) alone (500 μM), or SKF plus CGP. SKF increased both mean LH and LH pulse amplitude as compared with CSF. CGP alone had no significant effect on LH, but it attenuated the effect of SKF on mean LH. These observations indicate that the stimulatory effects of GABAB agonists on LH pulse patterns are mediated through GABAB receptors and provide further evidence that GABAB receptors located in the MBH can regulate pulsatile GnRH-LH release.