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

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.