Differences in ethanol ingestion between cholecystokinin-A receptor deficient and -B receptor deficient mice.
Differences in ethanol ingestion between cholecystokinin-A receptor deficient and -B receptor deficient mice.
复制标题
胆囊收缩素-A 受体缺陷型和胆囊收缩素-B 受体缺陷型小鼠之间乙醇摄入的差异。
作者：
K. Miyasaka;H. Hosoya;Saeko Takano;M. Ohta;Ayako Sekime;S. Kanai;T. Matsui;A. Funakoshi
目标
CCK通过CCK-A受体(CCK-AR)调节伏隔核多巴胺的释放。腹侧被盖区和边缘前脑之间的多巴胺能神经传递是酒精和药物自我给药的重要神经生物学成分。根据CCK与多巴胺相互作用的证据，我们已发现CCK-AR基因-81A/G多态性与酒依赖相关。由于这种关联的确切机制尚不清楚，我们利用CCK-AR基因缺陷(-/-)小鼠研究了CCK-AR在酒精摄取中的作用，并与CCK-BR(-/-)和野生型小鼠进行了比较。
方法
采用两瓶选择法，检测了这三种基因型的翻正反射。用免疫印迹法检测伏隔核多巴胺2受体(D2R)的蛋白水平。
结果
CCK-AR(-/-)小鼠比CCK-BR(-/-)和野生型小鼠消耗更多的乙醇，并且对高浓度的乙醇溶液没有表现出厌恶。然而，这种差异实际上是在总饮水量和饮酒偏好保持不变，表明这种差异并不是酒精所特有的。使用翻正反射检测的对酒精的行为敏感性在两组之间没有显著差异。CCK-BR(-/-)小鼠伏隔核D2R表达显著低于野生型小鼠，CCK-AR(-/-)小鼠D2R表达显著高于野生型小鼠。
结论
在CCK-AR(-/-)和CCK-BR(-/-)小鼠之间，自愿摄入酒精的情况不同。这种差异可能部分归因于伏隔核中D2R表达的不同水平。
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.
影响因子：
13.9
作者：
D. Self;Eric J. Nestler
通讯作者：
D. Self;Eric J. Nestler