RGD Reference Report - Is the Alcohol Deprivation Effect Genetically Mediated? Studies with HXB/BXH Recombinant Inbred Rat Strains. - Rat Genome Database

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Is the Alcohol Deprivation Effect Genetically Mediated? Studies with HXB/BXH Recombinant Inbred Rat Strains.

Authors: Vanderlinden, LA  Saba, LM  Printz, MP  Flodman, P  Koob, G  Richardson, HN  Hoffman, PL  Tabakoff, B 
Citation: Vanderlinden LA, etal., Alcohol Clin Exp Res. 2014 Jun 24. doi: 10.1111/acer.12471.
RGD ID: 8663441
Pubmed: PMID:24961585   (View Abstract at PubMed)
PMCID: PMC4142977   (View Article at PubMed Central)
DOI: DOI:10.1111/acer.12471   (Journal Full-text)

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).



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

QTLs
Alc24  (Alcohol consumption QTL 24)
Alc25  (Alcohol consumption QTL 25)
Alc26  (Alcohol consumption QTL 26)
Alc27  (Alcohol consumption QTL 27)
Alc28  (Alcohol consumption QTL 28)
Alc29  (Alcohol consumption QTL 29)
Alc30  (Alcohol consumption QTL 30)
Alc31  (Alcohol consumption QTL 31)
Alc32  (Alcohol consumption QTL 32)
Alc33  (Alcohol consumption QTL 33)
Alc34  (Alcohol consumption QTL 34)
Alc35  (Alcohol consumption QTL 35)
Alc36  (Alcohol consumption QTL 36)
Alc37  (Alcohol consumption QTL 37)

Strains
BXH/Ipcv  (NA)
HXB/Ipcv  (NA)

Objects referenced in this article
Marker rs105049829 rs105049829 Rattus norvegicus
Marker rs105560211 rs105560211 Rattus norvegicus
Marker rs64042903 rs64042903 Rattus norvegicus
Marker rs106547286 rs106547286 Rattus norvegicus
Marker rs63999739 rs63999739 Rattus norvegicus
Marker rs106373454 rs106373454 Rattus norvegicus
Marker rs105186122 rs105186122 Rattus norvegicus
Marker rs106860522 rs106860522 Rattus norvegicus
Marker rs65256837 rs65256837 Rattus norvegicus
Marker rs65621565 rs65621565 Rattus norvegicus
Marker rs107435003 rs107435003 Rattus norvegicus
Marker rs106844876 rs106844876 Rattus norvegicus
Marker rs107511300 rs107511300 Rattus norvegicus
Marker rs65015946 rs65015946 Rattus norvegicus
Marker rs106542192 rs106542192 Rattus norvegicus
Marker rs8143345 rs8143345 Rattus norvegicus
Marker rs64262745 rs64262745 Rattus norvegicus
Marker rs8170917 rs8170917 Rattus norvegicus
Marker rs107452597 rs107452597 Rattus norvegicus
Marker rs64209861 rs64209861 Rattus norvegicus
Marker rs105495306 rs105495306 Rattus norvegicus
Marker rs105776994 rs105776994 Rattus norvegicus
Marker rs65785626 rs65785626 Rattus norvegicus
Marker rs13455837 rs13455837 Rattus norvegicus
Marker rs106929875 rs106929875 Rattus norvegicus
Marker rs107439214 rs107439214 Rattus norvegicus
Marker rs107592435 rs107592435 Rattus norvegicus
Marker rs13452788 rs13452788 Rattus norvegicus
Marker rs107423234 rs107423234 Rattus norvegicus
Marker rs66395656 rs66395656 Rattus norvegicus
Marker rs107402384 rs107402384 Rattus norvegicus
Marker rs105497894 rs105497894 Rattus norvegicus
Marker rs64151264 rs64151264 Rattus norvegicus
Marker rs65296962 rs65296962 Rattus norvegicus
Marker rs8143351 rs8143351 Rattus norvegicus
Marker rs13448492 rs13448492 Rattus norvegicus
Marker rs64886957 rs64886957 Rattus norvegicus

Additional Information