title: Subjective Effects of Thiopental in Young Adults with and without a Family History of Alcoholism.
abstract: BACKGROUND
  The development of alcohol use disorders is genetically influenced, and may be mediated through differences in the subjective response to alcohol. There is some evidence to suggest that response differences to alcohol could be conveyed by heritable differences in GABAAreceptors. The purpose of this study was to investigate whether individuals with a family history positive (FHP) for alcohol dependence would experience alterations in response to the GABAAreceptor agonist thiopental, in comparison to family history negative (FHN) subjects.
  
  
  METHODS
  73 subjects (24 FHP and 49 FHN) between the ages of 21 and 30 years were administered sub-anesthetic doses of the GABAAreceptor agonist thiopental and placebo on two separate test days. Various alcohol-related measures were administered, including those examining subjective effects, coordination, and cognition.
  
  
  RESULTS
  Sub-anesthetic doses of thiopental produced alcohol-like subjective effects, as well as alcohol-like impaired coordination and cognition in healthy subjects. While there were no significant main effects in subjective, coordination, or cognitive effects between FHP and FHN individuals, analysis of peak effects suggested FHP had blunted sedative, but not stimulant effects compared to FHN.
  
  
  CONCLUSIONS
  Thiopental produced alcohol-like effects and perceived similarities to alcohol in healthy individuals. Subtle differences in sedative effects are consistent with reports of blunted FHP response to the negative but not stimulant effects of alcohol. Future studies are needed to better understand how this insight informs our understanding of the heritable risk for alcoholism and the treatment of alcohol use disorders.
authors.affiliation: NIAAA Center for the Translational Neuroscience of Alcoholism and Department of Psychiatry, Yale University School of Medicine, Connecticut, USA ; Department of Veterans Affairs, Alcohol Research Center, VA Connecticut Healthcare System, Connecticut, USA.
authors.forename: Ismene L
authors.initials: IL
authors.lastname: Petrakis
authors.forename: Karin
authors.initials: K
authors.lastname: Kerfoot
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: Albert
authors.initials: A
authors.lastname: Perrino
authors.forename: Julia
authors.initials: J
authors.lastname: Koretski
authors.forename: Jenelle
authors.initials: J
authors.lastname: Newcomb
authors.forename: Diana
authors.initials: D
authors.lastname: Limoncelli
authors.forename: Gregory
authors.initials: G
authors.lastname: Acampora
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ralevski
keywords: Alcohol; Family history; GABA; Thiopental; Vulnerability