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ORIGINAL ARTICLE

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

Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois 61802

The objectives of this study were to determine if the -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 co-infusion of the GABA_B 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] diethoxymethyl) 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 GABA_B agonists on LH pulse patterns are mediated through GABA_B receptors and provide further evidence that GABA_B receptors located in the MBH can regulate pulsatile GnRH-LH release.

Key Words: luteinizing hormone • GABA • male • sheep

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