Altered GABAA-benzodiazepine receptor number and pharmacology in the adult guinea pig cerebral cortex after chronic prenatal ethanol exposure

被引:17
作者
Bailey, CDC
Brien, JF
Reynolds, JN [1 ]
机构
[1] Queens Univ, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada
[2] Queens Univ, Dept Anaesthesia & Crit Care, Kingston, ON, Canada
关键词
GABA(A) receptor; cerebral cortex; guinea pig; prenatal ethanol exposure; benzodiazepine;
D O I
10.1097/00000374-199911000-00015
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
Background: The effects of chronic prenatal ethanol exposure on GABA(A)-benzodiazepine receptor number and binding pharmacology were examined in the cerebral cortex of the postnatal guinea pig. Methods: [H-3]Flunitrazepam binding to GABA(A)-benzodiazepine receptors was measured in a cerebral cortical cell membrane preparation obtained at postnatal days 11 (preweaning), 21 (postweaning), and 61 (adulthood). Zolpidem, a GABA(A)-benzodiazepine type 1 receptor-selective ligand, was used in a [H-3]flunitrazepam competition study. 3 alpha-Hydroxy-5 alpha-pregnan-20-one (allopregnanolone) potentiation of [H-3]muscismol [H-3]flunitrazepam binding, and GABA potentiation of [H-3]flunitrazepam binding were measured in these same animals. Results: At postnatal day 61, but not at the younger ages studied, the following was observed: (1) [H-3]Flunitrazepam binding exhibited an increased receptor number (B-max) and decreased affinity (increased K-D) in the ethanol-treated offspring compared with isocaloric-sucrose (with pair-feeding) and water-treated controls: and (2) the relative proportion of GABA(A)-benzodiazepine receptors that had high-affinity binding sites for zolpidem was decreased in the ethanol-treated offspring by 31% and 38% compared with the isocaloric-sucrose/pair-fed and water-treated controls, respectively. Chronic prenatal ethanol exposure did not alter the efficiency of coupling between GABA, benzodiazepine, and neurosteroid binding sires at any postnatal ages studied. Conclusions: These results suggest that, in the cerebral cortex of the adult guinea pig, chronic prenatal exposure to ethanol results in increased GABA(A)-benzodiazepine receptor number, decreased affinity for flunitrazepam, and decreased relative proportion of the GABA(A)-benzodiazepine type 1 receptor.
引用
收藏
页码:1816 / 1824
页数:9
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