Romieu Pascal, Gobaille Serge, Aunis Dominique, Zwiller Jean
INSERM, Unité 575, Centre de Neurochimie, Strasbourg, France.
Ann N Y Acad Sci. 2008 Oct;1139:27-33. doi: 10.1196/annals.1432.050.
Alcohol administration is known to alter several brain functions and behaviors in humans and in laboratory animals. One of the targets of ethanol is the mesocorticolimbic dopaminergic reward pathway. We used the "alcohol deprivation effect" test as a rat model of alcohol craving and relapse. The effect is characterized by increased alcohol intake and preference after several weeks of voluntary alcohol consumption followed by a withdrawal phase. The alcohol deprivation effect was found to be considerably reduced by the injection in dopaminergic brain structures of the neuropeptide CNP. This peptide is the most abundant natriuretic peptide in the brain, and signals via an intracellular rise in cyclic GMP. The effect of CNP was observed whether the peptide was injected in situ into the ventral tegmental area or into the prefrontal cortex. It was partially reversed by the injection in the same structures of KT5823, a selective inhibitor of the cGMP-dependent protein kinase. The results indicate that changes of cyclic GMP levels in dopaminergic rat brain areas participate in the neurobiological mechanisms underlying alcohol craving after withdrawal and/or alcohol dependence.
众所周知，饮酒会改变人类和实验动物的多种大脑功能及行为。乙醇的作用靶点之一是中脑皮质边缘多巴胺能奖赏通路。我们使用“戒酒效应”测试作为大鼠酒精渴望和复发的模型。该效应的特征是在几周的自愿饮酒后进入戒断阶段，酒精摄入量和偏好增加。研究发现，向多巴胺能脑区注射神经肽CNP可显著降低戒酒效应。这种肽是大脑中最丰富的利钠肽，通过细胞内环磷酸鸟苷（cGMP）水平升高来传递信号。无论将该肽原位注射到腹侧被盖区还是前额叶皮质，都能观察到CNP的作用。向相同脑区注射cGMP依赖性蛋白激酶的选择性抑制剂KT5823可部分逆转这种作用。结果表明，多巴胺能大鼠脑区中cGMP水平的变化参与了戒断后酒精渴望和/或酒精依赖背后的神经生物学机制。
