Journal
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
Volume 29, Issue 5, Pages 708-720Publisher
WILEY
DOI: 10.1097/01.ALC.0000164366.18376.EF
Keywords
dependence and withdrawal; soluble N-ethylmaleimide-sensitive factor attachment; protein receptor; vesicle release; Sec-1/Munc-18
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Funding
- NIAAA NIH HHS [P60 AA010760, AA11114, AA06243, AA10760] Funding Source: Medline
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Background: We previously mapped a quantitative trait locus (QTL) for ethanol preference drinking to mouse chromosome 2 (mapped with high confidence, LOD = 15.5,p 3 X 10(16)). The specific gene(s) in the QTL interval responsible for phenotypic variation in ethanol preference drinking has not been identified. Methods: In the current study, we investigated the association of the syntaxin binding protein 1 gene (Stxbp1) with ethanol preference drinking and other ethanol traits using a panel of B6 X D2 (BXD) recombinant inbred (RI) strains derived from the C57BL/6J (B6) and DBA/2J (B2) inbred mouse strains. Confirmation analyses for ethanol consumption and withdrawal were performed using a large B6D2 F-2 cross, short-term selected lines derived from the B6 and D2 progenitor strains, and standard inbred strains. Results: BXD RI strain analysis detected provisional associations between Stxbp1 molecular variants and ethanol consumption, as well as severity of acute ethanol withdrawal, ethanol-conditioned taste aversion, and ethanol-induced hypothermia. Confirmation analyses using three independent genetic models supported the involvement of Stxbp1 in ethanol preference drinking but not in ethanol withdrawal. Conclusions: Stxbp1 encodes a Sec1/Munc18-type protein essential for vesicular neurotransmitter release. The present study provides supporting evidence for the involvement of Stxbp1 in ethanol preference drinking.
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