Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice

Pharmacological blockade studies have supported a role of the dopamine syst em in ethanol reward for many years, but receptor subtype specificity has b een difficult to establish. Recently, genetically engineered mice lacking f unctional dopamine D2 receptors have been shown to drink less ethanol in a two-bottle choice task. To determine whether reduced ethanol intake reflect s a reduction in ethanol reward, D2 receptor-deficient [knockout (KO)] mice were compared to heterozygous (HET) and wild-type (WT; C57BL/6 x DBA/2 F2 hybrid) mice in a place conditioning task. Under conditions that produced r eliable place preference in both WT and HET mice, KO mice showed no evidenc e of place conditioning, suggesting that D2 receptor gene inactivation redu ced ethanol reward or the ability to learn about ethanol reward. Consistent with previous findings, this mutation also produced a gene dose-related re duction in basal activity levels. Moreover, KO and HET mice showed enhancem ent of ethanol-stimulated activity relative to WT mice. However, difference s in basal and ethanol-stimulated activity did not explain the differences in place conditioning. Overall, this study strongly supports the conclusion that dopamine D2 receptors normally influence ethanol reward in mice. (C) 2001 Elsevier Science Inc. All rights reserved.