title: Is the alcohol deprivation effect genetically mediated? Studies with HXB/BXH recombinant inbred rat strains.
abstract: BACKGROUND
  Two features of alcohol addiction that have been widely studied in animal models are relapse drinking following periods of alcohol abstinence and the escalation of alcohol consumption after chronic continuous or intermittent alcohol exposure. The genetic contribution to these phenotypes has not been systematically investigated.
  
  
  METHODS
  HXB/BXH recombinant inbred (RI) rat strains were given access to alcohol sequentially as follows: alcohol (10%) as the only fluid for 1 week; alcohol (10%) and water in a 2-bottle choice paradigm for 7 weeks ("pre-alcohol deprivation effect [ADE] alcohol consumption"); 2 weeks of access to water only (alcohol deprivation); and 2 weeks of reaccess to 10% alcohol and water ("post-ADE alcohol consumption"). The periods of deprivation and reaccess to alcohol were repeated 3 times. The ADE was defined as the amount of alcohol consumed in the first 24 hours after deprivation minus the average daily amount of alcohol consumed in the week prior to deprivation. Heritability of the phenotypes was determined by analysis of variance, and quantitative trait loci (QTLs) were identified.
  
  
  RESULTS
  All strains showed increased alcohol consumption, compared to the predeprivation period, in the first 24 hours after each deprivation (ADE). Broad-sense heritability of the ADEs was low (ADE1, 9.1%; ADE2, 26.2%; ADE3, 16.3%). Alcohol consumption levels were relatively stable over weeks 2 to 7. Post-ADE alcohol consumption levels consistently increased in some strains and were decreased or unchanged in others. Heritability of pre- and post-ADE alcohol consumption was high and increased over time (week 2, 38.5%; week 7, 51.1%; week 11, 56.8%; week 15, 63.3%). QTLs for pre- and post-ADE alcohol consumption were similar, but the strength of the QTL association with the phenotype decreased over time.
  
  
  CONCLUSIONS
  In the HXB/BXH RI rat strains, genotypic variance does not account for a large proportion of phenotypic variance in the ADE phenotype (low heritability), suggesting a role of environmental factors. In contrast, a large proportion of the variance across the RI strains in pre- and post-ADE alcohol consumption is due to genetically determined variance (high heritability).
authors: Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado.
authors: Lauren A
authors: LA
authors: Vanderlinden
authors: Laura M
authors: LM
authors: Saba
authors: Morton P
authors: MP
authors: Printz
authors: Pamela
authors: P
authors: Flodman
authors: George
authors: G
authors: Koob
authors: Heather N
authors: HN
authors: Richardson
authors: Paula L
authors: PL
authors: Hoffman
authors: Boris
authors: B
authors: Tabakoff
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology; D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics / Q000523:psychology; D002755:Choice Behavior; D005838:Genotype; D008297:Male; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics; D019655:Quantitative Trait, Heritable; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
keywords: Alcohol Consumption; Alcohol Deprivation Effect; HXB/BXH Recombinant Inbred Rat Strains; Heritability; Quantitative Trait Loci