Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D-2 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 sensi tivity of D-2-receptor-deficient mice to directly evaluate whether dopamine D-2 receptors contribute to alcohol (ethanol) consumption. We report a mar ked aversion to ethanol in these mice, relative to the high preference and consumption exhibited by wild-type littermates. Sensitivity to ethanol-indu ced locomotor impairment was also reduced in these mutant mice, although th ey showed a normal locomotor depressant response to the dopamine D-1 antago nist SCH-23390, These data demonstrate that dopamine signaling via D-2 rece ptors is an essential component of the molecular pathway determining ethano l self-administration and sensitivity.