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Behav Genet. 2003 May;33(3):311-24.

Effects of a Drd2 deletion mutation on ethanol-induced locomotor stimulation and sensitization suggest a role for epistasis.

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Veterans Affairs Medical Center, Research Service, Portland, Oregon 97239, USA.


Interpretation of studies using single gene mutants is complicated by possible epistatic interactions with genetic background. Dopamine D2 receptor (Drd2) knockout mice on a C57BL/6 (B6) background show decreased basal locomotion, ethanol preference and ethanol-induced ataxia. Epistatic interactions were studied by examining the effect of this null mutation on several traits on a B6 or 129S6 x 129S2 (129) background. Modification of the null mutant effect on ethanol preference by ethanol-induced locomotor sensitization was also examined in B6 background mice. B6 knockout mice exhibited enhanced ethanol-induced locomotor stimulation and sensitization. The reduced ethanol consumption observed in ethanol-naive B6 Drd2 knockout mice was absent in ethanol-sensitized knockout mice. Ethanol-induced locomotor stimulation was not enhanced in 129 knockout mice, and locomotor sensitization was only modestly increased. However, 129 null mutant mice exhibited reduced basal locomotion and diminished ethanol-induced ataxia, similar to our previous results in B6 mice. The impact of the Drd2 null mutation on a subset of ethanol-related behavioral traits is subject to epistatic influences.

[Indexed for MEDLINE]

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