Ogilvie K M, Rivier C
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Alcohol Clin Exp Res. 1997 May;21(3):424-9. doi: 10.1111/j.1530-0277.1997.tb03786.x.
Exposure of fetal rats to alcohol results in permanent hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In contrast, postnatal handling or fostering have been reported to restrain HPA activity. Because of the deleterious consequences of a hyperresponsive HPA axis, we thought that the possibility that postnatal manipulations might be able to reverse the influence of prenatal alcohol treatment deserved investigation. To test this hypothesis, we exposed rat dams to alcohol by inhalation during the second week of gestation. At birth, pups were either fostered or remained with their dam. For the first 3 weeks, litters were handled daily for 15 min or left undisturbed. At 22 days of age, male and female pups were decapitated under basal conditions, after 10 min of mild electro-footshock, or 10 min after footshock had been terminated. As expected, prenatal exposure to alcohol induced increased adrenocorticotropin (ACTH) secretion in response to footshock, and postnatal handling of control pups resulted in a suppression of corticosterone and ACTH release, although changes in this latter hormone did not reach statistical significance. Surprisingly, however, pups exposed to alcohol that were also fostered and handled after birth, showed an ACTH response to footshock stress that was significantly larger than all other groups. This unexpected response may be due to alterations in maternal-pup behaviors and may indicate that these manipulations act on different neuronal substrates within the central HPA of young rats. Further studies are needed to determine whether adrenal regulation is also altered in animals exposed to alcohol prenatally and reared in a similar manner.
将胎鼠暴露于酒精中会导致下丘脑 - 垂体 - 肾上腺（HPA）轴永久性亢进。相比之下，据报道出生后的抚摸或寄养可抑制HPA活性。由于HPA轴反应过度会产生有害后果，我们认为出生后的操作有可能逆转产前酒精治疗的影响，这一可能性值得研究。为了验证这一假设，我们在妊娠第二周通过吸入方式让孕鼠接触酒精。出生时，幼崽要么被寄养，要么仍与母鼠在一起。在最初的3周里，每天对一窝幼崽进行15分钟的抚摸，或者不进行干预。在22日龄时，在基础条件下、轻度电击足部10分钟后或电击足部结束10分钟后，将雄性和雌性幼崽断头处死。正如预期的那样，产前接触酒精会导致幼崽在受到电击时促肾上腺皮质激素（ACTH）分泌增加，对对照幼崽出生后的抚摸会导致皮质酮和ACTH释放受到抑制，尽管后一种激素的变化未达到统计学意义。然而，令人惊讶的是，出生后既被寄养又经过抚摸的酒精暴露幼崽，对电击应激的ACTH反应明显大于所有其他组。这种意外反应可能是由于母 - 幼行为的改变，并且可能表明这些操作作用于幼鼠中枢HPA内不同的神经元底物。需要进一步研究以确定产前暴露于酒精并以类似方式饲养的动物中肾上腺调节是否也发生改变。
