Altered stress responsiveness in adult rats exposed to ethanol in utero: neuroendocrine mechanisms.
Altered stress responsiveness in adult rats exposed to ethanol in utero: neuroendocrine mechanisms.
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子宫内暴露于乙醇的成年大鼠的应激反应性改变：神经内分泌机制。
DOI：
10.1002/9780470720868.ch4
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Poland,RE
中科院分区：
文献类型：
--
作者：
Taylor,AN;Nelson,LR;Branch,BJ;Kokka,N;Poland,RE
在我们的第一项研究中，下丘脑-垂体-肾上腺（HPA）轴的活性被发现在对某些应激源（包括乙醇）的反应中，在胎儿暴露于乙醇的成年大鼠（胎儿乙醇暴露[FEE]大鼠）中比在成对喂养衍生或正常对照中显着更大。通过测量不可避免的足电击后应激诱导的镇痛，进一步检查FEE大鼠的应激反应。在成年FEE大鼠中，通过长时间/间歇性纳洛酮可逆形式的足电击增强了镇痛作用，但通过短暂/连续纳洛酮不敏感形式则没有增强镇痛作用，这表明该作用是阿片类药物介导的。成年FEE大鼠表现出更大的镇痛和血浆皮质酮反应吗啡的挑战比对照组大鼠。初步结果还表明，当成年FEE大鼠每天暴露于间歇性足电击应激（10分钟/天）时，它们消耗的乙醇显著多于对照组。通过测量FEE和对照新生儿脑和血浆皮质酮含量，确定是否改变了应激反应反映了胎儿乙醇诱导的HPA轴发育效应。出生时，FEE幼崽的全脑和血浆皮质酮水平显著升高。在出生后第7天，当基础血浆皮质酮浓度已达到正常值，FEE大鼠显示迟钝的皮质酮响应乙醇管理，表明持续影响的胎儿乙醇暴露，尽管其终止前一周。这些新生儿激素变化对胎儿乙醇暴露对应激反应的长期影响的确切贡献仍有待确定。
In our first studies the activity of the hypothalamo-pituitary-adrenal (HPA) axis was found to be significantly greater in response to certain stressors, including ethanol, in adult rats exposed to ethanol as fetuses (fetal ethanol-exposed [FEE] rats) than in pair-fed-derived or normal controls. Stress responsiveness in FEE rats was examined further by measuring stress-induced analgesia after inescapable footshock. Analgesia was enhanced in adult FEE rats by a prolonged/intermittent naloxone-reversible form of footshock, but not by a brief/continuous naloxone-insensitive form, suggesting that the effect was opioid-mediated. Adult FEE rats showed greater analgesic and plasma corticosterone responses to morphine challenges than control rats. Preliminary results also indicated that when adult FEE rats were exposed daily to the intermittent footshock stress (10 min/day) they consumed significantly more ethanol than controls. Whether the altered stress responsiveness reflects fetal ethanol-induced effects on the development of the HPA axis was determined by measuring brain and plasma content of corticosterone in FEE and control neonates. At birth, in FEE pups, whole brain and plasma corticosterone levels are significantly raised. On postnatal day 7, when basal plasma corticosterone concentrations have attained normal values, FEE rats display blunted corticosterone responses to ethanol administration, indicating persistent effects of the fetal ethanol exposure despite its termination one week previously. The precise contribution of these neonatal hormonal alterations to the long-term effects of fetal ethanol exposure on stress responsiveness remains to be determined.