Region-specific down-regulation of Crhr1 gene expression in alcohol-preferring msP rats following ad lib access to alcohol
Region-specific down-regulation of Crhr1 gene expression in alcohol-preferring msP rats following ad lib access to alcohol
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DOI：
10.1111/j.1369-1600.2007.00050.x
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Heilig, Markus
中科院分区：
文献类型：
--
作者：
Hansson, Anita C.;Cippitelli, Andrea;Heilig, Markus
促肾上腺皮质激素释放激素1受体（CRH-R1）介导依赖史后对压力和过量酒精自我管理的行为敏感性增加。最近的研究表明，遗传选择的酒精偏好msP大鼠系复制了许多特征的后依赖状态，由于先天上调的Crhr 1转录在几个边缘系统领域相关的饮酒动机。在这里，我们研究了是否自愿饮酒可能能够下调Crhr 1转录水平在msP大鼠在大脑区域的表达升高，以前已被证明。在中央和内侧杏仁核（CeA，MeA），以及Nc。Accumbens，2周的自由饮酒导致Crhr 1转录的高度显著下调。酒精诱导的Crhr 1下调在扣带回皮质中没有观察到。这些数据支持扩展杏仁核组件内CRH-R1信号传导的招募驱动过量的酒精摄入，并且酒精自愿消费部分是因为其能够降低该区域的CRH-R1活性。
Corticotropin-releasing hormone 1 receptors (CRH-R1) mediate increased behavioral sensitivity to stress and excessive alcohol self-administration following a history of dependence. It was recently demonstrated that the genetically selected alcohol-preferring msP rat line replicates many characteristics of the post-dependent state, due to an innate up-regulation of the Crhr1 transcript in several limbic areas related to alcohol drinking motivation. Here, we examined whether voluntary alcohol consumption might be able to down-regulate Crhr1 transcript levels in msP rats in brain areas where elevated expression previously has been shown. Within central and medial amygdala (CeA, MeA), as well as the Nc. Accumbens, 2 weeks' ad lib access to alcohol led to a highly significant down-regulation of the Crhr1 transcript. Alcohol-induced Crhr1 down-regulation was not seen in cingulate cortex. These data support that recruitment of CRH-R1 signaling within components of the extended amygdala drives excessive alcohol intake, and that alcohol is voluntarily consumed in part for its ability to reduce CRH-R1 activity in this region.