Pilot 6 - Developmental Exposure Alcohol Research Center

试点 6 - 发育性暴露酒精研究中心

• 批准号: 8381971
• 负责人: JILLA SABETI
• 金额: $ 1.16万
• 依托单位: STATE UNIVERSITY OF NY,BINGHAMTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8381971
• 关键词: 4-Aminobutyrate aminotransferase; Adult Children; Alcohol consumption; Alphaxolone; Barbiturates; Behavioral; Benzodiazepines; Biological Assay; Brain; Carboxy-Lyases; Cerebellum; Chloride Ion; Chlorides; Data; Development; Drug Receptors; Ethanol; Exhibits; Exposure to; Fetal Alcohol Exposure; Flurazepam; GABA transporter; Goals; Hippocampus (Brain); Hour; In Vitro; Literature; Mediation; Membrane; Messenger RNA; Modeling; Mothers; Mus; Mutant Strains Mice; Pentobarbital; Pharmaceutical Preparations; Pregnancy; Role; System; Time; Transcript; adolescent offspring; alcohol research; alcohol sensitivity; barbituric acid salt; base; gamma-Aminobutyric Acid; human TFRC protein; hypnotic; mRNA Expression; neurosteroids; postnatal; pregnant; prenatal; prenatal exposure; receptor; receptor expression; receptor function; receptor sensitivity

We have recently taken advantage of a new limited access model of binge-like ethanol intake to expose pregnant C57BL6/J mice to ethanol for 2 hours each day throughout gestation. Daily maternal ethanol intakes of 5-6 g/kg produced a number of behavioral deficits in adult and adolescent offspring. In particular, hypnotic sensitivity to ethanol was reduced at postnatal day (P) 30 and P90 (p<0.01) possibly suggesting that prenatal ethanol exposure alters the normal development GABAA receptor systems. The goals of this proposal are to (1) determine whether maternal DID alters hypnotic and GABAA receptor sensitivity to several drugs with actions at the receptor and (2) to examine the expression of various GABAA receptor subunits in the adolescent and adult offspring of these mice.

我们最近利用了一种新的狂饮乙醇摄入有限模型来揭露 怀孕的 C57BL6/J 小鼠在整个妊娠期间每天摄入乙醇 2 小时。每日母亲乙醇摄入量 5-6克/公斤的剂量会导致成年和青少年后代出现许多行为缺陷。尤其是催眠药 对乙醇的敏感性在产后第 30 天和第 90 天降低（p<0.01），这可能表明产前 乙醇暴露会改变 GABAA 受体系统的正常发育。该提案的目标是 (1)确定母体DID是否改变催眠药和GABAA受体对几种有作用药物的敏感性 (2) 检查青少年中各种 GABAA 受体亚基的表达 这些小鼠的成年后代。