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

Abraham A. Palmer, Malcolm J. Low, David Grandy, Tamara Phillips

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 129S6×129S2 (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-naïve 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.

Original languageEnglish (US)
Pages (from-to)311-324
Number of pages14
JournalBehavior Genetics
Volume33
Issue number3
DOIs
StatePublished - May 2003

Fingerprint

epistasis
Sequence Deletion
ethanol
mutation
Ethanol
Knockout Mice
mice
locomotion
Ataxia
Locomotion
mutants
effect
sequence deletion
129 Strain Mouse
Mutation
Dopamine D2 Receptors
dopamine
genetic background

Keywords

  • Alcoholism
  • Ataxia
  • Dopamine
  • Drinking
  • Epistasis
  • Knockout

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Behavioral Neuroscience
  • Psychology(all)

Cite this

Effects of a Drd2 deletion mutation on ethanol-induced locomotor stimulation and sensitization suggest a role for epistasis. / Palmer, Abraham A.; Low, Malcolm J.; Grandy, David; Phillips, Tamara.

In: Behavior Genetics, Vol. 33, No. 3, 05.2003, p. 311-324.

Research output: Contribution to journalArticle

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