• S R Singh and K P Briski.
• Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health Sciences, University of Louisiana Monroe, Monroe, LA 71209, USA.
• J. Neuroendocrinol. 2005 Jul 1;17(7):407-12.

AbstractThe neurochemical mechanisms that link caudal hindbrain glucoprivic-'sensitive' neurones with the forebrain gonadotrophin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) axis remain unclear. Available studies indicate that the amino acid neurotransmitter, gamma-aminobutyric acid (GABA), inhibits reproductive neuroendocrine function, and that caudal fourth ventricular administration of the glucose antimetabolite, 5-thioglucose (5TG), enhances GABA turnover within discrete septopreoptic structures that regulate LH secretion. The current experiments utilized the selective GABA(A) and GABA(B) receptor antagonists, bicuculline and phaclofen, as pharmacological tools to investigate whether one or both receptor subtypes function within neural pathways that suppress GnRH neuronal transcriptional activation and LH release during central glucose deficiency. During the ascending phase of the afternoon LH surge, groups of steroid-primed, ovariectomized female Sprague-Dawley rats were pretreated by lateral ventricular administration of bicuculline, phaclofen, or vehicle only, before fourth ventricular injection of 5TG or vehicle. The data indicate that, 2 h after 5TG treatment, Fos immunoexpression by rostral preoptic GnRH neurones and plasma LH levels were diminished relative to the vehicle-treated controls, and that inhibitory effects of 5TG on these parameters were attenuated by pretreatment with bicuculline, but not phaclofen. These results demonstrate that central GABA(A), but not GABA(B) receptor stimulation during hindbrain glucoprivation, is required for maximal inhibition of reproductive neuroendocrine function by this metabolic challenge. The current studies thus reinforce the view that central GABAergic neurotransmission mediates regulatory effects of central glucoprivic signalling on the GnRH-pituitary LH axis.

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