Activation of gamma-aminobutyric acid B-receptors abolishes naloxone-stimulated luteinizing hormone release.
Recent evidence suggests that the neurotransmitter gamma-aminobutyric acid (GABA) plays an important role in the control of gonadotropin secretion. The present study was conducted to identify the effect and site of action of different GABAergic drugs on LH secretion in vivo and to characterize the precise roles of different GABA receptors in these actions. Three different GABAergic drugs were used: muscimol and baclofen, which act at the level of the GABA A- and GABA B-receptors, respectively, and aminooxyacetic acid (AOAA), which increases the GABA content in the brain. The effects of these drugs were investigated in situations of enhanced LH secretion due to administration of naloxone or LHRH. In an initial experiment, adult male rats were treated ip with AOAA, followed by naloxone. AOAA treatment decreased basal LH levels and prevented naloxone-stimulated LH release. PRL levels were decreased by either AOAA or naloxone; however, the combination of these two drugs did not induce an additional or synergistic effect on the decreased PRL levels. In subsequent experiments, freely moving rats bearing Silastic cannulae in the right jugular vein received AOAA, muscimol, or baclofen a few minutes before either naloxone or LHRH administration. Baclofen and AOAA completely suppressed the naloxone-stimulated LH increase. Muscimol did not prevent the effect of naloxone. None of the three GABAergic drugs affected LH release in rats receiving LHRH. The results of these in vivo experiments suggest that the GABAergic system exerts primarily an inhibitory effect on gonadotropin secretion which is mediated at a central level, since pituitary responsiveness to LHRH is not affected by GABAergic drug treatment. GABA B-receptors are responsible for the inhibitory action of GABA.
Masotto
C
C
Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Negro-Vilar
A
A
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D011963:Receptors, GABA-A; D000625:Aminooxyacetic Acid; D009118:Muscimol; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D011388:Prolactin; D007986:Luteinizing Hormone; D001418:Baclofen