Intensification of the development of ethanol dependence in mice lacking dopamine D(3) receptor.
The present study was designed to ascertain the role of dopamine D3 receptors in the development of physical dependence on ethanol using mice lacking the dopamine D3 receptor gene. The mutation eliminated the dopamine D3 receptor without any detectable changes in both dopamine D1 and D2 receptors. The ethanol-induced sleep time in dopamine D3 receptor knockout mice (D3-KO) was longer than that in wild-type mice. To examine the role of dopamine D3 receptors in the development of physical dependence on ethanol, two genotypes were chronically treated with 7% ethanol according to the liquid diet method. After the termination of ethanol treatment, severe withdrawal signs were observed in D3-KO mice as compared with wild-type mice. The present data suggest that the lack of dopamine D3 receptor genes in the mouse brain leads to the aggravation of the development of physical dependence on ethanol.
Narita
Minoru
M
Department of Toxicology, School of Pharmacy, Hoshi University, 2-4-41 Ebara Shinagawa-Ku, Tokyo 142-8501, Japan.
Soma
Miho
M
Tamaki
Hiroko
H
Narita
Michiko
M
Suzuki
Tsutomu
T
D020268:Alcohol-Induced Disorders, Nervous System / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics; D050637:Receptors, Dopamine D3; D012890:Sleep / Q000187:drug effects / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
C493594:Drd3 protein, mouse; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000431:Ethanol; D004298:Dopamine