title: Gamma-aminobutyric acid-A and -B receptor antagonists increase luteinizing hormone-releasing hormone neuronal responsiveness to intracerebroventricular norepinephrine in ovariectomized estrogen-treated rats.
abstract: These studies determined whether endogenous gamma-aminobutyric acid (GABA) secretion affects LHRH neuronal responsiveness to norepinephrine (NE). The intracerebroventricular (icv) infusion of either bicuculline or phaclofen (GABA-A or GABA-B receptor antagonists, respectively) into ovariectomized (OVX) estrogen-treated rats did not affect basal LH levels (95 +/- 8.5 ng/ml) obtained over the 120 min of this study. When NE was infused icv, it produced a modest rise in plasma LH, which peaked within 15 min (240 +/- 25 ng/ml) and then declined toward baseline over the next 90 min. In contrast, if bicuculline was given icv at about time zero, and NE was infused (icv) 15 min later, plasma LH secretion was markedly increased and reached a peak concentration of 723 +/- 98 ng/ml within 15 min after NE treatment. Similarly, when bicuculline was infused into the medial preoptic area (MPOA), and NE was given 15 min later (icv), a peak LH level of 726 +/- 105 ng/ml was obtained within 15 min. If phaclofen was given icv at about time zero, and NE was infused 15 min later, LH rose dramatically to reach a peak concentration of 844 +/- 126 ng/ml within 15 min; a similar amplified LH response occurred when the GABA-B antagonist was infused into the MPOA and icv NE was given 15 min later. Comparisons of the LH responses obtained over the 120 min of the study suggest that icv infusions of the GABA-B receptor antagonist were more effective in sustaining peak LH secretion than the GABA-A receptor antagonist. In other groups of rats, the MPOA was electrochemically stimulated (ECS), and the effects of icv NE alone or combined with GABA receptor antagonists were evaluated. MPOA ECS alone induced a significant rise in plasma LH, which peaked between 35-45 min and then declined to approach basal levels by 150 min. In a second group, the MPOA was ECS, and at 30 min NE was infused icv. Plasma LH levels in these rats remained significantly elevated for the next 30 min before beginning their decline. In other animals, the MPOA was stimulated, and 15 min later either bicuculline or phaclofen was infused icv. Neither drug affected the patterns or concentrations of LH obtained after MPOA ECS alone. However, when rats received MPOA ECS plus either icv bicuculline or phaclofen, and these treatments were followed 15 min later by icv infusions of NE, LH secretion patterns and levels were altered significantly.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Physiology, University of Maryland, Baltimore 21201.
authors.forename: R D
authors.initials: RD
authors.lastname: Hartman
authors.forename: J R
authors.initials: JR
authors.lastname: He
authors.forename: C A
authors.initials: CA
authors.lastname: Barraclough
mesh_terms: D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism*; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D010052:Ovariectomy; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; C052329:phaclofen; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D007986:Luteinizing Hormone; D001418:Baclofen; D009638:Norepinephrine; D001640:Bicuculline