GABA Mechanisms Underlying the Vulnerability to Alcohol Dependence
Condition: Alcoholism
MeSH terms: Alcoholism
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Thiopental; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): A 2-day test design involving 2 conditions: saline (Placebo) or Thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion).; A 2-day test design involving 2 conditions: saline (Placebo) or Thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion).
Intervention MeSH terms: Thiopental
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Health Services Research
Keywords: Thiopental; Alcohol; Family History; Vulnerability; GABA