van Oers H J, de Kloet E R, Levine S
Department of Psychology, University of Delaware, Newark, DE, USA.
J Neuroendocrinol. 1999 Aug;11(8):581-8. doi: 10.1046/j.1365-2826.1999.00329.x.
Maternal deprivation of neonatal rats for 24 h has immediate and persistent effects on hypothalamic-pituitary-adrenal (HPA) regulation. Immediately after deprivation corticosterone (CORT) is elevated. The primary purpose of our experiments was to determine if, by preventing this CORT elevation, the persistent effects could be reversed. In experiment 1, pups were injected with dexamethasone at the onset of the 24-h deprivation period on postnatal day 11 to suppress the rise in CORT. In experiment 2 some aspects of maternal behaviour known to suppress CORT levels were mimicked during deprivation from postnatal days 11-12. The pups were either: (1) left undisturbed; (2) stroked periodically; or (3) stroked and episodically fed. At postnatal day 20 basal and stress-induced adrenocorticotrophic hormone (ACTH) and CORT levels were measured as well as brain mineralocorticoid (MR) and glucocorticoid receptors (GR). Neonatal rats receiving dexamethasone prior to the onset of the deprivation on day 11 did not differ on day 20 from deprived pups that were exposed to elevated CORT levels. There were no detectable changes in the non-deprived pups that were treated with dexamethasone. In contrast, feeding and stroking during the period of deprivation obliterated the persistent effects both with regard to the reduced ACTH response and the decreased GR mRNA in hippocampus and hypothalamus. Stroking alone appears to have no influence. In conclusion, the persistent reduction of the ACTH response to mild stress and the decrease of GR mRNA is not mediated by deprivation-induced elevations in CORT, but appears to be reversible by reinstating specific aspects of the dam's nurturing behaviour.
新生大鼠出生后24小时母婴分离对下丘脑-垂体-肾上腺(HPA)轴调节有即时和持续的影响。分离后即刻,皮质酮(CORT)水平升高。我们实验的主要目的是确定通过阻止CORT水平升高,是否能逆转其持续影响。在实验1中,在出生后第11天24小时分离期开始时给幼崽注射地塞米松,以抑制CORT升高。在实验2中,在出生后第11至12天的分离期间模拟一些已知可抑制CORT水平的母性行为。幼崽被分为:(1)不打扰;(2)定期抚摸;或(3)抚摸并偶尔喂食。在出生后第20天测量基础和应激诱导的促肾上腺皮质激素(ACTH)和CORT水平,以及脑盐皮质激素(MR)和糖皮质激素受体(GR)。在第11天分离开始前接受地塞米松的新生大鼠在第20天与暴露于升高CORT水平的分离幼崽没有差异。接受地塞米松治疗的未分离幼崽没有可检测到的变化。相比之下,在分离期间喂食和抚摸消除了对应激反应降低以及海马体和下丘脑GR mRNA减少的持续影响。单独抚摸似乎没有影响。总之,ACTH对轻度应激反应的持续降低和GR mRNA的减少不是由分离诱导的CORT升高介导的,而是通过恢复母鼠养育行为的特定方面似乎可以逆转。