Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors

Tamara J. Phillips, Kelly J. Brown, Sue Burkhart-Kasch, Charlotte D. Wenger, Michele A. Kelly, Marcelo Rubinstein, David Grandy, Malcolm J. Low

Research output: Contribution to journalArticlepeer-review

218 Scopus citations


Although dopaminergic transmission has been strongly implicated in alcohol self-administration, the involvement of specific dopamine receptor subtypes has not been well established. We studied the ethanol preference and sensitivity of D2-receptor-deficient mice to directly evaluate whether dopamine D2 receptors contribute to alcohol (ethanol) consumption. We report a marked aversion to ethanol in these mice, relative to the high preference and consumption exhibited by wild-type littermates. Sensitivity to ethanol-induced locomotor impairment was also reduced in these mutant mice, although they showed a normal locomotor depressant response to the dopamine D1 antagonist SCH-23390. These data demonstrate that dopamine signaling via D2 receptors is an essential component of the molecular pathway determining ethanol self-administration and sensitivity.

Original languageEnglish (US)
Pages (from-to)610-615
Number of pages6
JournalNature Neuroscience
Issue number7
StatePublished - Nov 1998

ASJC Scopus subject areas

  • Neuroscience(all)


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