Gabriel K I, Yu W, Ellis L, Weinberg J
Department of Anatomy, University of British Columbia, Vancouver, Canada.
Alcohol Clin Exp Res. 2000 Oct;24(10):1566-74.
Prenatal ethanol exposure results in hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stress in the adult animal. In contrast, an early environmental manipulation, termed "postnatal handling," has been shown to result in decreased and/or less prolonged HPA activity in response to moderate stressors throughout the lifespan of the animal. The effects of both prenatal ethanol exposure and postnatal handling on HPA activity may be mediated by altered feedback regulation of the HPA axis. The present study tested the hypothesis that postnatal handling could attenuate the impact of prenatal ethanol exposure on hormonal responses to stressors.
Male and female Sprague Dawley rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) groups were either handled (H) or nonhandled (NH) during the preweaning period and were tested at 4 to 5 months of age. Animals were subjected to a 60 min restraint stress, 3 hr after intraperitoneal injection with either saline (SAL) or a synthetic glucocorticoid, dexamethasone-21-phosphate (DEX), in order to examine HPA responsiveness after DEX blockade of endogenous HPA activity. Blood samples were collected via jugular cannulae immediately before restraint (0 min), during restraint (10, 30, and 60 min), and 30 min after the termination of restraint (90 min).
For both males and females, DEX administration significantly reduced plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations compared with SAL administration. H animals showed greater suppression of HPA activity (i.e., lower ACTH and/or CORT levels) than NH animals regardless of prenatal group. In addition, E females from both the H and NH treatments showed elevated ACTH and CORT after both SAL and DEX administration, whereas H and NH E males showed elevations in ACTH and CORT only after SAL, compared with their PF and C counterparts.
These data extend results from previous studies that demonstrated HPA hyperresponsiveness in E animals. The finding that E females but not males exhibit elevated ACTH and CORT after DEX administration suggests that prenatal ethanol exposure results in sex-specific alterations of HPA feedback. Consistent with previous data, handling in itself reduced the HPA response to restraint stress. However, handling did not attenuate either HPA hyperresponsiveness or feedback deficits in E animals.
产前乙醇暴露会导致成年动物下丘脑 - 垂体 - 肾上腺（HPA）轴对应激的反应过度。相比之下，一种早期环境干预措施，即“产后抚触”，已被证明在动物的整个生命周期中，能使HPA轴在面对中度应激源时活动减少和/或持续时间缩短。产前乙醇暴露和产后抚触对HPA轴活动的影响可能是由HPA轴反馈调节的改变介导的。本研究检验了以下假设：产后抚触可以减弱产前乙醇暴露对应激源激素反应的影响。
将产前乙醇暴露组（E）、配对喂食组（PF）和自由进食对照组（C）的雄性和雌性Sprague Dawley大鼠在断奶前进行抚触（H）或不进行抚触（NH）处理，并在4至5月龄时进行测试。动物在腹腔注射生理盐水（SAL）或合成糖皮质激素地塞米松 - 21 - 磷酸酯（DEX）3小时后，接受60分钟的束缚应激，以检查在DEX阻断内源性HPA轴活动后HPA轴的反应性。在束缚前（0分钟）、束缚期间（10、30和60分钟）以及束缚结束后30分钟（90分钟），通过颈静脉插管采集血样。
对于雄性和雌性动物，与注射SAL相比，注射DEX显著降低了血浆促肾上腺皮质激素（ACTH）和皮质酮（CORT）浓度。无论产前分组如何，接受抚触的动物（H）比未接受抚触的动物（NH）对HPA轴活动的抑制作用更强（即ACTH和/或CORT水平更低）。此外，与PF组和C组的雌性相比，接受抚触和未接受抚触处理的产前乙醇暴露组（E）雌性在注射SAL和DEX后ACTH和CORT均升高，而接受抚触和未接受抚触处理的产前乙醇暴露组（E）雄性仅在注射SAL后ACTH和CORT升高。
这些数据扩展了先前研究的结果，即产前乙醇暴露的动物中HPA轴反应过度。产前乙醇暴露组（E）雌性在注射DEX后ACTH和CORT升高，而雄性未出现这种情况，这一发现表明产前乙醇暴露导致了HPA轴反馈的性别特异性改变。与先前数据一致，抚触本身可降低HPA轴对束缚应激的反应。然而，抚触并未减弱产前乙醇暴露组（E）动物的HPA轴反应过度或反馈缺陷。
