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Alcohol and Alcoholism Advance Access published online on March 14, 2005
Alcohol and Alcoholism, doi:10.1093/alcalc/agh143
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Alcohol & Alcoholism © Medical Council on Alcohol 2005; all rights reserved
Received July 13, 2004
Revised September 29, 2004
Accepted February 17, 2005

Article

DIFFERENCES IN ETHANOL INGESTION BETWEEN CHOLECYSTOKININ-A RECEPTOR DEFICIENT AND -B RECEPTOR DEFICIENT MICE

KYOKO MIYASAKA 1*, HIROKO HOSOYA 1, SAEKO TAKANO 1, MINORU OHTA 1, AYAKO SEKIME 1, SETSUKO KANAI 1, TOSHIMITSU MATSUI 2, and AKIHIRO FUNAKOSHI 3

1 Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho Itabashiku, Tokyo 173-0015, Japan
2 Third Division, Department of Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan
3 Division of Gastroenterology, National Kyushu Cancer Center, Fukuoka 811-1395, Japan

* To whom correspondence should be addressed.
KYOKO MIYASAKA, E-mail: miyasaka{at}tmig.or.jp


  Abstract

Aims: Cholecystokinin (CCK) modulates dopamine release in the nucleus accumbens through the CCK-A receptor (CCK-AR). The dopaminergic neurotransmission between the ventral tegmental area and the limbic forebrain is a critical neurobiological component of alcohol and drug self-administration. Based on the evidence of interaction between CCK and dopamine, we had found previously that the CCK-AR gene -81A/G polymorphism was associated with alcohol dependence. Since the precise mechanism underlying this association has not been elucidated, the role of CCK-AR in ethanol ingestion was examined using CCK-AR gene deficient (-/-) mice and compared with those of CCK-BR(-/-) and wild-type mice. Methods: The two-bottle choice protocol was conducted and the righting reflex was examined in these three genotypes. Furthermore, the protein level of dopamine 2 receptor (D2R) in the nucleus accumbens was determined by western blotting. Results: CCK-AR(-/-) mice consumed more ethanol than CCK-BR(-/-) and wild-type mice, and showed no aversion to high concentrations of ethanol solution. However, the difference was actually in the total fluid consumption and alcohol preference remained unchanged, indicating that the differences were not specific to alcohol. Behavioral sensitivity to ethanol, examined using the righting reflex, did not differ significantly between the groups. D2R expression in the nucleus accumbens was significantly lower in the CCK-BR(-/-) mice and was significantly higher in CCK-AR(-/-) mice than in wild-type mice. Conclusions: Voluntary ingestion of ethanol differed between CCK-AR(-/-) and CCK-BR(-/-) mice. The difference might be attributable in part to the different levels of D2R expression in the nucleus accumbens.


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