Exposure to alcohol during adolescence exerts long-term effects on stress response and the adult brain stress circuits.
Exposure to alcohol during adolescence exerts long-term effects on stress response and the adult brain stress circuits.
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DOI：
10.1016/j.neuroscience.2016.09.031
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发表时间：
2016-12-17
期刊：
影响因子：
3.3
通讯作者：
Lee S
中科院分区：
文献类型：
--
作者：
Allen CD;Grigoleit JS;Hong J;Bae S;Vaughan J;Lee S
下丘脑-垂体-肾上腺（HPA）轴在青春期经历了关键的发展。因此，在此期间经历的压力可能对成人HPA轴功能产生长期影响。我们假设青少年间歇性乙醇（AIE）暴露会影响成人HPA轴功能，导致年轻人或成年人对酒精挑战的反应发生改变。为了检验这些假设，雄性大鼠从出生后第28-42天（PND）每天暴露于酒精蒸汽6小时，然后在年轻成年人（PND 70）或成年人（PND 90）中用酒精灌胃（3.2-4.5 g/kg）进行急性激发。总的来说，我们观察到钝化HPA轴响应酒精挑战由于AIE曝光。具体而言，AIE倾向于抑制酒精攻击诱导的血浆皮质酮（CORT）浓度在年轻的成年和成年大鼠的增加。同时，AIE显著减弱了成年大鼠下丘脑室旁核（PVN）中酒精激发诱导的精氨酸加压素（Avp）mRNA表达。本研究的结果是类似的，我们以前已经表明，这些变化PVN的反应可能会导致AIE诱导的改变，肾上腺素能神经元在脑干C1-C3已知项目的PVN。AIE增加了成年大鼠C1区c-fos/PNMT阳性胞体的数量。总之，这些数据表明，AIE暴露产生的男性HPA轴的响应管理的急性酒精挑战，可能是持久的改变。
The hypothalamic-pituitary-adrenal (HPA) axis undergoes critical developments during adolescence. Therefore, stressors experienced during this period potentially have long-term effects on adult HPA axis function. We hypothesized that adolescent intermittent ethanol (AIE) exposure would affect adult HPA axis function, resulting in altered responses to an alcohol challenge in young adults or adults. To test these hypotheses, male rats were exposed to alcohol vapor for 6 h per day from post-natal day (PND) 28–42, then acutely challenged with alcohol intragastrically (3.2–4.5 g/kg) in young adults (PND 70) or adults (PND 90). Overall, we observed blunted HPA axis responses to an alcohol challenge due to AIE exposure. Specifically, AIE tended to inhibit the alcohol-challenge-induced increase in plasma corticosterone (CORT) concentrations in young adult and adult rats. As well, AIE significantly blunted the alcohol challenge-induced arginine vasopressin (Avp) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus of adult rats. Results of the present study are similar to what we have previously shown, that these changes in PVN responsiveness may result from AIE-induced alterations in adrenergic neurons in brain stem regions C1–C3 known to project to the PVN. AIE elevated the number of colocalized c-fos/phenylethanolamine N-methyltransferase (PNMT)-positive cell bodies in the C1 region of adult rats. Together, this data suggests that AIE exposure produces alterations in male HPA axis responsiveness to administration of an acute alcohol challenge that may be long-lasting.