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.
Phillips
T J
TJ
Department of Veterans Affairs Medical Center, Portland, Oregon 97201, USA. phillipt@ohsu.edu
Brown
K J
KJ
Burkhart-Kasch
S
S
Wenger
C D
CD
Kelly
M A
MA
Rubinstein
M
M
Grandy
D K
DK
Low
M J
MJ
D000428:Alcohol Drinking / Q000503:physiopathology; D000818:Animals; D020296:Animals, Congenic; D001552:Benzazepines / Q000494:pharmacology; D002755:Choice Behavior / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000172:deficiency* / Q000502:physiology
D001552:Benzazepines; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D000431:Ethanol