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首页> 外文期刊>International Journal of Environmental Research and Public Health >Αlpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats
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Αlpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats

机译：α2a-肾上腺素能受体基因表达与早期生命应激介导的近交大鼠饮酒倾向

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Stressful events early in life, later high alcohol consumption and vulnerability to alcohol use disorder (AUD) are tightly linked. Norepinephrine is highly involved in the stress response and the α2A-adrenoceptor, which is an important regulator of norepinephrine signalling, is a putative target in pharmacotherapy of AUD. The aim of the present study was to investigate the effects of early-life stress and adult voluntary alcohol drinking on the α2A-adrenoceptor. The relative expression and promoter DNA methylation of the Adra2a gene were measured in the hypothalamus, a key brain region in stress regulation. A well-characterized animal model of early-life stress was used in combination with an episodic voluntary drinking in adulthood. Alcohol drinking rats with a history of early-life stress had lower Adra2a expression than drinking rats not exposed to stress. Alcohol intake and Adra2a gene expression were negatively correlated in high-drinking animals, which were predominantly rats subjected to early-life stress. The results provide support for a link between early-life stress, susceptibility for high alcohol consumption, and low Adra2a expression in the hypothalamus. These findings can increase our understanding of the neurobiological basis for vulnerability to initiate risk alcohol consumption and individual differences in the response to α2A-adrenoceptor agonists.
机译：生活中的压力事件，后来的高饮酒量和易患酒精滥用症（AUD）紧密相关。去甲肾上腺素高度参与应激反应，而α2A-肾上腺素受体是去甲肾上腺素信号传导的重要调节剂，是AUD药物治疗的假定靶点。本研究的目的是研究早期生活压力和成人自愿饮酒对α2A-肾上腺素能受体的影响。在下丘脑中测量了Adra2a基因的相对表达和启动子DNA甲基化，下丘脑是压力调节的关键大脑区域。一个成熟的早期应激动物模型与成年期发作性自愿饮酒结合使用。具有早期生活压力史的饮酒大鼠比未遭受压力的饮酒大鼠具有较低的Adra2a表达。高饮动物的饮酒量与Adra2a基因表达呈负相关，而高饮动物主要是遭受早年应激的大鼠。这些结果为生命早期压力，高饮酒敏感性和下丘脑中Adra2a低表达之间的联系提供了支持。这些发现可以增进我们对神经生物学基础的认识，这些神经生物学基础是引发酒精消费风险的脆弱性以及对α2A-肾上腺素受体激动剂反应的个体差异。

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