Effects of a Drd2 deletion mutation on ethanol-induced locomotor stimulation and sensitization suggest a role for epistasis.
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.
Palmer
Abraham A
AA
Veterans Affairs Medical Center, Research Service, Portland, Oregon 97239, USA.
Low
Malcolm J
MJ
Grandy
David K
DK
Phillips
Tamara J
TJ
D000428:Alcohol Drinking / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004843:Epistasis, Genetic; D000431:Ethanol / Q000494:pharmacology*; D017353:Gene Deletion; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D009154:Mutation; D017448:Receptors, Dopamine D2 / Q000235:genetics*
D017448:Receptors, Dopamine D2; D000431:Ethanol