Zagron Gal, Weinstock Marta
Department of Pharmacology, School of Pharmacy, Hebrew University Medical Centre, Ein Kerem, Jerusalem 92110, Israel.
Behav Brain Res. 2006 Dec 15;175(2):323-8. doi: 10.1016/j.bbr.2006.09.003. Epub 2006 Oct 4.
Prenatal stress in rats has been shown to impair the regulation of the hypothalamic pituitary adrenal (HPA) axis and predispose to anxiogenic and depressive-like behaviour. In a previous study, abolition of excess corticosterone (COR) release during stress by maternal adrenalectomy prevented the dysregulation of the HPA axis. In the present study, we determined whether excess maternal COR is also responsible for the alterations in offspring behaviour. Pregnant Wistar rats were adrenalectomized or sham-operated on day 11 of gestation and subjected once daily to mild restraint for 30 min on days 14-21 of gestation. An undisturbed group of pregnant females served as controls. All experiments were performed in male and female offspring. Pup weight and anogenital distance of males were measured after birth; anxiogenic behaviour was assessed in the elevated plus maze (EPM) at the age of 5 weeks and spatial memory in the Morris water maze in littermates at 3-4 months. Prenatally stressed (PS) males did not show a reduction in anogenital distance, and their increase in anxiogenic behaviour in the EPM was less than that in PS females. On the other hand, impairment of spatial learning was only seen in PS males. Both the anxiogenic behaviour of PS males and females and the learning deficit in males were completely abolished by adrenalectomy. These data show that excess stress-induced COR can alter the programming of the foetal brain and predispose it to alterations in behaviour that are gender specific.
研究表明,大鼠孕期应激会损害下丘脑 - 垂体 - 肾上腺(HPA)轴的调节功能,并易引发焦虑样和抑郁样行为。在先前的一项研究中,通过母体肾上腺切除术消除应激期间过量的皮质酮(COR)释放,可防止HPA轴失调。在本研究中,我们确定过量的母体COR是否也与后代行为的改变有关。妊娠第11天,对怀孕的Wistar大鼠进行肾上腺切除术或假手术,并在妊娠第14 - 21天每天对其进行一次30分钟的轻度束缚。一组未受干扰的怀孕雌性大鼠作为对照。所有实验均在雄性和雌性后代中进行。出生后测量雄性幼崽的体重和肛门生殖器距离;在5周龄时在高架十字迷宫(EPM)中评估焦虑样行为,在3 - 4个月时在同窝幼崽的莫里斯水迷宫中评估空间记忆。产前应激(PS)雄性大鼠的肛门生殖器距离没有减小,并且它们在EPM中焦虑样行为的增加小于PS雌性大鼠。另一方面,空间学习障碍仅在PS雄性大鼠中出现。肾上腺切除术完全消除了PS雄性和雌性大鼠的焦虑样行为以及雄性大鼠的学习缺陷。这些数据表明,过量的应激诱导COR可改变胎儿大脑的编程,并使其易发生特定性别的行为改变。