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

Abstract

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.

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Figure 1: Ethanol consumption and preference are markedly reduced in dopamine D2-receptor-deficient mice.
Figure 2: Saccharin and quinine preference are unaffected by the absence of functional D2 dopamine receptors.
Figure 3: Dopamine D2-receptor-deficient mice are insensitive to the locomotor depressant effects of ethanol.
Figure 4: Dopamine D2-receptor-deficient mice show reduced sensitivity to ethanol-induced ataxia.
Figure 5: Locomotor depressant response to the dopamine D1 antagonist SCH-23390 is normal in dopamine D2-receptor-deficient mice.

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Acknowledgements

We thank Dr. John Crabbe for his suggested revisions of an earlier version of this manuscript. These studies were supported by a grant from the Department of Veterans Affairs (T.J.P.), by grants P50 AA10760 (T.J.P.,M.J.L.,D.K.G.), T32 AA07468 (T.J.P.), T32 DA07262 (M.A.K.), R21 DA09620 (D.K.G.), R01 DA12062 (D.K.G.) and by an International Research Scholar grant of the HHMI (M.R.).

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Correspondence to Tamara J. Phillips.

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Phillips, T., Brown, K., Burkhart-Kasch, S. et al. Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors. Nat Neurosci 1, 610–615 (1998). https://doi.org/10.1038/2843

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