Taylor A N, Nelson L R, Branch B J, Kokka N, Poland R E
Ciba Found Symp. 1984;105:47-65. doi: 10.1002/9780470720868.ch4.
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.
在我们最初的研究中，发现与配对喂养的对照组或正常对照组相比，在胎儿期接触乙醇的成年大鼠（胎儿乙醇暴露 [FEE] 大鼠）中，下丘脑 - 垂体 - 肾上腺（HPA）轴对某些应激源（包括乙醇）的反应活性显著更高。通过测量不可逃避的足部电击后应激诱导的镇痛作用，进一步研究了 FEE 大鼠的应激反应性。成年 FEE 大鼠通过长时间/间歇性纳洛酮可逆形式的足部电击增强了镇痛作用，但短暂/持续的纳洛酮不敏感形式则没有，这表明该效应是由阿片类药物介导的。成年 FEE 大鼠对吗啡激发的镇痛和血浆皮质酮反应比对照大鼠更大。初步结果还表明，当成年 FEE 大鼠每天暴露于间歇性足部电击应激（每天 10 分钟）时，它们消耗的乙醇比对照组显著更多。通过测量 FEE 和对照新生大鼠大脑和血浆中皮质酮的含量，确定了应激反应性的改变是否反映了胎儿乙醇对 HPA 轴发育的影响。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达到正常值时，FEE 大鼠对乙醇给药的皮质酮反应减弱，这表明尽管胎儿乙醇暴露在一周前已经终止，但其仍有持续影响。这些新生儿激素变化对胎儿乙醇暴露对应激反应性长期影响的确切作用仍有待确定。
