Evidence for gamma-aminobutyric acid modulation of ovarian hormonal effects on luteinizing hormone secretion and hypothalamic catecholamine activity in the female rat.
Recent evidence suggests that gamma-aminobutyric acid (GABA)-containing neurons may inhibit LH release under certain circumstances. The present experiments tested whether GABA agonists block the LH surge induced in ovariectomized rats by estradiol benzoate (EB) plus progesterone (P) treatment and whether these agents affect the concentration and turnover of hypothalamic catecholamines, assessed from the depletion that occurs after synthesis inhibition. Ovariectomized rats received EB, followed 2 days later by P. Simultaneously with P, rats received either saline or one of the GABA agonists, baclofen or muscimol. Other agonist-treated rats received a second injection 4 h later or were additionally treated with the postsynaptic GABA antagonist bicuculline. Additional experiments tested the effects of these agents on LH release in response to exogenous LHRH. The LH surge induced by EB plus P was blocked by administration of either baclofen or muscimol in a dose-dependent manner. Bicuculline did not prevent the effect of baclofen, but partially prevented the effect of muscimol. Neither baclofen nor muscimol significantly affected LH release in rats receiving LHRH. In a second set of studies in EB plus P-treated rats, baclofen and muscimol decreased the steady state concentrations of norepinephrine in the medial preoptic area and medial basal hypothalamus for several hours and markedly decreased the turnover rate of norepinephrine in these areas. The concentrations and turnover of epinephrine were also decreased by these GABA agonists in the medial basal hypothalamus. The drugs had no effect on dopamine levels or turnover in either structure. These results support the hypothesis that a GABAergic system regulates LH release via modulation of noradrenergic and adrenergic systems that control LHRH secretion.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002369:Castration; D002395:Catecholamines / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D008781:Methyltyrosines / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D019805:alpha-Methyltyrosine; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002395:Catecholamines; D008781:Methyltyrosines; D009118:Muscimol; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D019805:alpha-Methyltyrosine; D007986:Luteinizing Hormone; D001418:Baclofen; D009638:Norepinephrine; D001640:Bicuculline; D004837:Epinephrine