title: Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking.
abstract: BACKGROUND
  Subjective perceptions of alcohol intoxication are associated with altered risk for alcohol abuse and dependence. Acute adaptation of these perceptions may influence such risk and may involve genes associated with pleasant perceptions or the relief of anxiety. This study assessed the effect of variation in the GABAA receptor genes GABRG1 and GABRA2 and recent drinking history on the acute adaptation of subjective responses to alcohol.
  
  
  METHODS
  One hundred and thirty-two nondependent moderate to heavy drinkers, aged 21 to 27, participated in 2 single-blind, counterbalanced sessions, approximately 1 week apart. One session was an intravenous alcohol "clamp," during which breath alcohol concentration was held steady at 60 mg/dl (60 mg%) for 3 hours, and the other an identical session using saline infusion. Subjective perceptions of Intoxication, Enjoyment, Stimulation, Relaxation, Anxiety, Tiredness, and Estimated Number of Drinks were acquired before (baseline), and during the first and final 45 minutes of the clamp. A placebo-adjusted index of the subject's acute adaptation to alcohol was calculated for each of the 7 subjective measures and used in a principal component analysis to create a single aggregate estimate for each subject's adaptive response to alcohol. Analysis of covariance tested whether GABRA2 and GABRG1 single nucleotide polymorphism (SNP) genotypes, gender, placebo session, family history of alcoholism, recent drinking history, and the genotype × recent drinking history interaction significantly predicted the adaptive response.
  
  
  RESULTS
  Recent drinking history (p = 0.01), and recent drinking history × genotype interaction (p = 0.01) were significantly associated with acute adaptation of the subjective responses to alcohol for the GABRA2 SNP rs279858.
  
  
  CONCLUSIONS
  Higher recent drinking was found to be associated with reduced acute tolerance to positive, stimulating effects of alcohol in carriers of the rs279858 risk allele. We postulate that the GABRA2 effect on alcohol dependence may, in part, be due to its effect on subjective responses to alcohol.
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Ann E K
authors.initials: AE
authors.lastname: Kosobud
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.|Department of Psychology, Indiana University Purdue University at Indianapolis, Indianapolis, Indiana.
authors.forename: Leah
authors.initials: L
authors.lastname: Wetherill
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Plawecki
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: David A
authors.initials: DA
authors.lastname: Kareken
authors.affiliation: Department of Medicine, Division of Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Tiebing
authors.initials: T
authors.lastname: Liang
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: John L
authors.initials: JL
authors.lastname: Nurnberger
authors.affiliation: Department of Psychology, Indiana University Purdue University at Indianapolis, Indianapolis, Indiana.
authors.forename: Kyle
authors.initials: K
authors.lastname: Windisch
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xuei
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Howard J
authors.identifier: http://orcid.org/0000-0003-0344-9690
authors.initials: HJ
authors.lastname: Edenberg
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Foroud
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Administration Medical Center, Indianapolis, Indiana.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: O'Connor
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000328:Adult; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011963:Receptors, GABA-A / Q000235:genetics*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D002492:Central Nervous System Depressants; C484841:GABRA2 protein, human; C546279:GABRG2 protein, human; D011963:Receptors, GABA-A; D000431:Ethanol
keywords: Acute Tolerance; Alcohol Use Disorders; Family History of Alcoholism; GABA Receptors; Intravenous Alcohol