Gamma-Aminobutyric Acid (GABA) Mechanisms Underlying the Vulnerability to Alcohol Dependence

Yale University1 个研究点分布在 1 个国家目标入组 73 人开始时间: 2005年11月最近更新: 2017年3月17日

适应症

干预措施

试验速览

阶段: 不适用
状态: 已完成
发起方: Yale University
入组人数: 73
试验地点: 1
主要终点: Visual Analog Scales of Similarity to Alcohol - 45 Minutes

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This Project will explore the hypothesis that individuals with a family history positive for alcohol dependence (without any current Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABAA receptor agonist barbiturate (thiopental) compared to family history negative age-matched subjects. Further, variation in genes involved in brain GABA function may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.

详细描述

This project will explore the hypothesis that individuals with a family history positive for alcohol dependence (FHP) (without any current DSM-IV Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABA-A receptor agonist barbiturate (thiopental) compared to family history negative (FHN) age-matched subjects. Further, the effect of variations in genes important in regulating brain GABA function may alter a component of the discriminative stimulus effects of ethanol. FHP individuals are defined as individuals with at least one first-degree relative and another first- or second-degree relatives. Preliminary results suggest that FHP individuals showed an attenuated response to thiopental as measured by the descending limb of the BAES during thiopental infusion relative to the FHN group. Further, preliminary results suggest that variation in genes involved in brain GABA function, glutamate decarboxylase-65 (GAD65), may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.

We plan to recruit 2 groups of healthy subjects between the ages of 21-30, one with a family history of alcoholism (family history positive=FHP) and a sex-matched control group without a family history of alcoholism (family history negative=FHN), to undergo two test days scheduled 3 days apart, in a randomized double-blind fashion. Test days will involve a 60-minute intravenous infusion of each of 2 conditions: saline or thiopental, in a randomized order under double-blind conditions. Behavioral ratings include the Biphasic Alcohol Effects Scale (BAES) and Visual Analog Scales (VAS). Exploratory measures include event-related potential recordings (ERP) and measures of eye-to-hand coordination. Blood will be collected for Deoxyribonucleic acid (DNA) extraction and genotyping.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Health Services Research
盲法: Double (Participant, Outcomes Assessor)

入排标准

年龄范围: 21 Years 至 30 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•Male and female between the ages of 21 and 30 years
•medically and neurologically healthy on the basis of history, physical examination, Electrocardiogram (EKG), screening laboratories
•absence of any evidence of substance abuse (with the exception of nicotine dependence) on the basis of history and drug and ethanol-free at the time of testing based on urine toxicology and breath alcohol levels at screening and on each test day.

排除标准

•Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) Axis I psychiatric and substance abuse or dependence diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (SCID)
•unwillingness to remain alcohol-free for three days prior to each test day;
•for women, positive pregnancy test at screening or intention to engage in unprotected sex during the study and
•alcohol naive. For Family History Positive Subjects: 1) Biological father and another first or second-degree biological relative with history of alcoholism by Family History Assessment Module (FHAM) developed by The Collaborative Study on the Genetics of Alcoholism (COGA).
•For Family History Negative Subjects: NO family history of alcoholism in any first or second-degree relatives. Subjects must reliably report on three first-degree relatives.

研究组 & 干预措施

Family History Negative for Alcoholism

Active Comparator

Family History Negative for Alcoholism subjects will receive 2 interventions

干预措施: Thiopental (Drug)

Family History Positive for Alcoholism

Placebo Comparator

Family History Positive for Alcoholism subjects will receive 2 interventions

干预措施: Placebo (Drug)