Merali Z, Hayley S, Kent P, McIntosh J, Bédard T, Anisman H
University of Ottawa, Department of Psychology, Ottawa, Ontario, K1N 6N5, Canada.
Behav Brain Res. 2009 Mar 2;198(1):105-12. doi: 10.1016/j.bbr.2008.10.025. Epub 2008 Oct 30.
Repeated exposure to stressors was reported to increase the expression of arginine-vasopressin (AVP), especially in corticotropin-releasing hormone (CRH) neurons co-expressing AVP, within the hypothalamus. This may increase the potential for subsequent stressor-elicited enhancement of hypothalamic-pituitary-adrenal (HPA) functioning as these peptides synergistically stimulate pituitary ACTH secretion. Likewise, members of the bombesin (BB) family of peptides (including its mammalian analogues gastrin-releasing peptide (GRP) and neuromedin B (NMB)) stimulate the release of ACTH and may play a role in the mediation and/or modulation of the CRH stress response. In the present investigation, chronic stressor exposure (daily restraint over 14 days) was associated with increased co-expression of CRH and AVP at the median eminence. In addition, in vivo interstitial levels of anterior pituitary AVP, GRP and NMB (but not CRH) were elevated following chronic stressor exposure. Basal pituitary corticosterone levels, in contrast, were unaffected by chronic stressor exposure. Following consumption of a highly palatable snack, interstitial levels of CRH, GRP, NMB and corticosterone (but not AVP) were elevated at the pituitary; however, a cross-sensitization was not apparent among rats previously exposed to the stressor and then provided with the snack. As the CRH, AVP and BB-like peptide systems have been associated with altered anxiety and depressive symptoms, the sustained peptidergic alterations observed in the chronically stressed rats may have implications for the development of these stressor-related disorders.
据报道,反复暴露于应激源会增加精氨酸加压素(AVP)的表达,尤其是在下丘脑内共表达AVP的促肾上腺皮质激素释放激素(CRH)神经元中。这可能会增加随后应激源引起的下丘脑-垂体-肾上腺(HPA)功能增强的可能性,因为这些肽协同刺激垂体促肾上腺皮质激素(ACTH)的分泌。同样,蛙皮素(BB)家族的肽(包括其哺乳动物类似物胃泌素释放肽(GRP)和神经降压素B(NMB))成员刺激ACTH的释放,并可能在CRH应激反应的介导和/或调节中发挥作用。在本研究中,慢性应激源暴露(14天每日束缚)与正中隆起处CRH和AVP的共表达增加有关。此外,慢性应激源暴露后,垂体前叶AVP、GRP和NMB(但不包括CRH)的体内间质水平升高。相比之下,基础垂体皮质酮水平不受慢性应激源暴露的影响。食用高度可口的零食后,垂体处CRH、GRP、NMB和皮质酮(但不包括AVP)的间质水平升高;然而,在先前暴露于应激源然后提供零食的大鼠中,交叉致敏并不明显。由于CRH、AVP和BB样肽系统与焦虑和抑郁症状的改变有关,在慢性应激大鼠中观察到的持续性肽能改变可能与这些应激源相关疾病的发展有关。