PRENATAL ETHANOL--EFFECT ON LATER ETHANOL RESPONSIVENESS

产前乙醇——对以后乙醇反应的影响

• 批准号: 3111666
• 负责人: HOWARD C. BECKER
• 金额: $ 11万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3111666
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; behavior disorders; blood chemistry; central nervous system; drug metabolism; drug tolerance; embryo /fetus drug adverse effect; ethanol; genetic strain; growth /development; inhalation drug administration; laboratory mouse; longitudinal animal study; mature animal; neurochemistry; neuromuscular disorder; pharmacology; prenatal stress; psychopharmacology; alcoholic beverage consumption; alcoholism /alcohol abuse; behavior disorders; blood chemistry; central nervous system; drug metabolism; drug tolerance; embryo /fetus drug adverse effect; ethanol; genetic strain; growth /development; inhalation drug administration; laboratory mouse; longitudinal animal study; mature animal; neurochemistry; neuromuscular disorder; pharmacology; prenatal stress; psychopharmacology

While a growing body of literature has characterized the physiological and morphological consequences of prenatal ethanol (EtOH) exposure, few studies have examined the influence of such prenatal treatment on subsequent responsiveness to EtOH challenge. Moreover, there is a clear void in the literature pertaining to the influence of prenatal EtOH exposure on subsequent responsiveness to chronic EtOH treatment, particularly as such treatment relates to the development of tolerance and dependence. Given the anomalies in neurochemistry, neuroanatomy, endocrinology, and behavior reported in animals exposed to EtOH prenatally, combined with preliminary data from our laboratory, there is good reason to hypothesize that group differences in EtOH sensitivity should be observed. The general hypothesis being tested is that animals exposed to EtOH in utero will differ from controls in subsequent response to acute and chronic EtOH challenge. To test this hypothesis, a total of ten studies have been designed to investigate the influence of prenatal EtOH exposure on subsequent postnatal sensitivity to (1) acute EtOH challenge, (2) the development and expression of EtOH tolerance, and (3) the development and expression of physical dependence. More specifically, a mouse model system will be used to determine whether prenatal EtOH exposure effects acute sensitivity to EtOH-induced stimulation prenatal EtOH exposure effects acute sensitivity to EtOH- induced stimulation of locomotor activity and EtOH-induced motor incoordination, the development and/or expression of tolerance to the motor incoordinating action of EtOH, and development and/or expression of EtOH dependence, as assessed by intensity of the withdrawal response. Further, additional studies are aimed at identifying potential neurochemical mechanisms underlying altered CNS sensitivity to acute and chronic EtOH challenge by employing a psychopharmacologic approach. Taken together, these studies will fill a critical void in the fetal EtOH literature and begin to address possible CNS mechanisms underlying alteration in neurosensitivity to EtOH in offspring exposed to EtOH in utero.

虽然越来越多的文献表征了生理学 和产前乙醇（ETOH）暴露的形态学后果，很少 研究检查了这种产前治疗对 随后对ETOH挑战的反应。而且，还有一个清晰的 与产前ETOH的影响有关的文献中的空白 随后对慢性ETOH治疗的反应性暴露， 特别是由于这种治疗与耐受性的发展有关 和依赖。鉴于神经化学的异常，神经解剖学， 内分泌学和暴露于EtOH的动物中报告的行为 产前，与我们实验室的初步数据相结合，有 有充分的理由假设ETOH灵敏度的群体差异 应该观察到。 一般的假设正在检验 在随后对急性的响应中，子宫与对照组有所不同， 慢性ETOH挑战。为了检验这一假设，总共十项研究 旨在研究产前ETOH暴露的影响 随后对（1）急性EtoH挑战的产后敏感性，（2） ETOH耐受性的发展和表达，以及（3）发展和 身体依赖的表达。 更具体地说，鼠标模型系统将用于确定是否是否 产前ETOH暴露对ETOH诱导的急性敏感性 刺激产前ETOH暴露对ETOH的急性敏感性 引起的运动活性刺激和ETOH诱导的电动机 对耐受性的不协调，发展和/或表达 ETOH的运动不协调的动作以及开发和/或表达 ETOH依赖依赖性，如戒断反应的强度所评估。 此外，其他研究旨在确定潜力 基于中枢神经系统对急性的敏感性改变了神经化学机制 通过采用心理药物方法来挑战慢性ETOH挑战。 综上所述，这些研究将填充胎儿EtoH中的关键空隙 文学并开始解决可能的中枢神经系统机制 暴露于EtOH的后代的神经敏感性改变了EtOH 子宫。