TY - JOUR
T1 - Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice
AU - Cunningham, Christopher L.
AU - Howard, MacKenzie A.
AU - Gill, Sylvia J.
AU - Rubinstein, Marcelo
AU - Low, Malcolm J.
AU - Grandy, David K.
N1 - Funding Information:
This research was supported in part by grants AA10760, AA07468, AA07702 and DA12062. Thanks are extended to Tamara Phillips for her comments on the manuscript.
PY - 2000
Y1 - 2000
N2 - Pharmacological blockade studies have supported a role of the dopamine system in ethanol reward for many years, but receptor subtype specificity has been difficult to establish. Recently, genetically engineered mice lacking functional dopamine D2 receptors have been shown to drink less ethanol in a two-bottle choice task. To determine whether reduced ethanol intake reflects a reduction in ethanol reward, D2 receptor-deficient [knockout (KO)] mice were compared to heterozygous (HET) and wild-type (WT; C57BL/6 × DBA/2 F2 hybrid) mice in a place conditioning task. Under conditions that produced reliable place preference in both WT and HET mice, KO mice showed no evidence of place conditioning, suggesting that D2 receptor gene inactivation reduced ethanol reward or the ability to learn about ethanol reward. Consistent with previous findings, this mutation also produced a gene dose-related reduction in basal activity levels. Moreover, KO and HET mice showed enhancement of ethanol-stimulated activity relative to WT mice. However, differences 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.
AB - Pharmacological blockade studies have supported a role of the dopamine system in ethanol reward for many years, but receptor subtype specificity has been difficult to establish. Recently, genetically engineered mice lacking functional dopamine D2 receptors have been shown to drink less ethanol in a two-bottle choice task. To determine whether reduced ethanol intake reflects a reduction in ethanol reward, D2 receptor-deficient [knockout (KO)] mice were compared to heterozygous (HET) and wild-type (WT; C57BL/6 × DBA/2 F2 hybrid) mice in a place conditioning task. Under conditions that produced reliable place preference in both WT and HET mice, KO mice showed no evidence of place conditioning, suggesting that D2 receptor gene inactivation reduced ethanol reward or the ability to learn about ethanol reward. Consistent with previous findings, this mutation also produced a gene dose-related reduction in basal activity levels. Moreover, KO and HET mice showed enhancement of ethanol-stimulated activity relative to WT mice. However, differences 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.
KW - C57BL/6×DBA/2 F2 hybrid mice
KW - Conditioned place preference
KW - Dopamine D2 receptor
KW - Ethanol
KW - Knockout mice
KW - Locomotor activity
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U2 - 10.1016/S0091-3057(00)00414-7
DO - 10.1016/S0091-3057(00)00414-7
M3 - Article
C2 - 11166059
AN - SCOPUS:0034486288
SN - 0091-3057
VL - 67
SP - 693
EP - 699
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 4
ER -