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Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation

机译:自愿饮酒对长期暴露于母体分离的成年雄性大鼠中皮层皮质大脑中毛Mao表达的影响

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摘要

Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption affect Maoa expression in stress- and reward-related brain regions in the rat. Outbred Wistar rats were exposed to rearing conditions associated with stress (prolonged maternal separation) or no stress during early life, and given free choice between alcohol and/or water in adulthood. Transcript levels of Maoa were assessed in the ventral tegmental area, nucleus accumbens (NAc), medial prefrontal cortex, cingulate cortex, amygdala and dorsal striatum (DS). Blood was collected to assess corticosterone levels. After alcohol consumption, lower blood corticosterone and Maoa expression in the NAc and DS were found in rats exposed to early life stress compared with control rats. An interaction between early life stress and voluntary alcohol intake was found in the NAc. Alcohol intake before death correlated negatively with Maoa expression in DS in high alcohol-drinking rats exposed to early life stress. Maoa expression is sensitive to adulthood voluntary alcohol consumption in the presence of early life stress in outbred rats. These findings add knowledge of the molecular basis of the previously reported associations between early life stress, MAOA and susceptibility to alcohol misuse.
机译:在人类和非人类的灵长类动物中,单胺氧化酶A(MAOA)基因型与高饮酒之间存在不一致的关联。环境影响可能是中等遗传敏感性。这种相互作用的生物学基础仍然难以捉摸,并且不一致要求进行翻译研究,在该研究中可以控制条件并且可以接近脑组织。本研究调查了早期生活压力和随后的成年流行性饮酒是否会影响大鼠与压力和奖赏相关的大脑区域中的Maoa表达。近交Wistar大鼠在生命早期处于与压力相关的饲养条件下(母体分离时间较长)或没有压力,成年后可在酒精和/或水之间自由选择。在腹侧被盖区,伏隔核(NAc),内侧前额叶皮层,扣带回皮层,杏仁核和背侧纹状体(DS)中评估Maoa的转录水平。收集血液以评估皮质酮水平。饮酒后,与对照组相比,在处于早期生活压力的大鼠中,NAc和DS中的血液皮质酮和毛那木表达较低。在NAc中发现了早期生活压力和自愿饮酒之间的相互作用。饮酒前死亡的高饮大鼠中,死亡前的饮酒与DS中Maoa表达负相关。在近亲大鼠存在生命早期应激的情况下,Maoa表达对成年期自愿饮酒敏感。这些发现增加了先前报道的早期生活压力,MAOA和滥用酒精敏感性之间的关联的分子基础知识。

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