Involvement of cholecystokinin-A receptor function in alcohol drinking behavior

Abstract

CCK modulates dopamine release in the nucleus accumbens via the CCK-A receptor (R). The dopaminergic neurotransmission between the ventral tegmental area and the limbic forebrain is a critical neurobiological component of alcohol and drug self-administration. We previously found that the CCK-AR gene -81A/G polymorphism was associated with alcohol dependence (Alco & Alco 2004). In the present study, the role of CCK-AR in ethanol ingestion was examined using CCK-AR gene deficient (KO) mice. The two-bottle choice protocol (ethanol, saccharin, and quinine) was conducted and the righting reflex was examined. The protein level of dopamine 2 receptor (D2R) in the nucleus accumbens as well as dopamine content in the brain were determined. The spontaneous activities were recorded at 1-minute intervals using a biotelemetry system. CCK-ARKO mice consumed more ethanol than 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. Ethanol metabolism and dopamine content did not differ significantly between the groups. D2R expression in the nucleus accumbens was significantly higher in CCK-ARKO mice than in wild-type mice. The activity during the night-time was significantly higher in CCK-ARKO mice than in wild-type mice. The difference in voluntary ingestion of ethanol might be attributable in part to different levels of D2R expression in the nucleus accumbens as well as to different levels of spontaneous activities. [Jpn J Physiol 55 Suppl:S201 (2005)]