Chronic mild stress induces behavioral and physiological changes, and may alter serotonin 1A receptor function, in male and cycling female rats
Chronic mild stress induces behavioral and physiological changes, and may alter serotonin 1A receptor function, in male and cycling female rats
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DOI：
10.1007/s00213-004-2103-4
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发表时间：
2005-06-01
影响因子：
3.4
通讯作者：
de Kar, LDV
中科院分区：
文献类型：
--
作者：
Grippo, AJ;Sullivan, NR;de Kar, LDV
应激、5 - 羟色胺1A（5 - HT1A）受体和下丘脑 - 垂体 - 肾上腺皮质（HPA）系统之间的相互作用被认为会影响人类抑郁症的发展。在抑郁症动物模型中对与抑郁症相关的行为以及对环境应激源的生理反应进行研究，可能会为这些机制提供有价值的见解。这些实验的目的是在一种抑郁症动物模型——慢性轻度应激（CMS）中研究中枢5 - HT1A受体、内分泌功能和行为之间的相互作用。本研究检测了在暴露于4周CMS的雄性和雌性大鼠中，在全身给予一种选择性5 - HT1A受体激动剂[（+）8 - 羟基 - N，N - 二丙基 - 2 - 氨基四氢萘氢溴酸盐（8 - OH - DPAT）；40μg/kg，皮下注射；在处死前15分钟给药]后，对一种愉悦刺激（蔗糖）的行为反应、发情周期长度（雌性大鼠）以及血浆激素水平。4周的CMS导致1%蔗糖摄入量减少（快感缺失），并且雄性和雌性大鼠对8 - OH - DPAT的促肾上腺皮质激素（ACTH）反应减弱（分别比对照组低22%和18%）。皮质酮和催产素对8 - OH - DPAT的反应不受CMS暴露的影响。在雌性大鼠中，CMS导致发情周期延长约40%。CMS会产生轻微的HPA紊乱以及行为紊乱。中枢神经系统中特定神经元群体的5 - HT1A受体功能改变可能与CMS模型有关。目前的研究结果有助于我们理解应激和神经内分泌功能与抑郁症之间的关系。
Interactions among stress, serotonin 1A (5-HT1A) receptors, and the hypothalamic-pituitary-adrenocortical (HPA) system have been proposed to influence the development of depression in humans. The investigation of depression-relevant behaviors and physiological responses to environmental stressors in animal models of depression may provide valuable insight regarding these mechanisms. The purpose of these experiments was to investigate the interactions among central 5-HT1A receptors, endocrine function, and behavior in an animal model of depression, chronic mild stress (CMS). The current study examined behavioral responses to a pleasurable stimulus (sucrose), estrous cycle length (in female rats), and plasma hormone levels following systemic administration of a selective 5-HT1A receptor agonist [(+)8-hydroxy-N,N-dipropyl-2-aminotetralin hydrobromide (8-OH-DPAT); 40 mu g/kg, s.c.; administered 15min prior to sacrifice], in male and female rats exposed to 4 weeks of CMS. Four weeks of CMS produced a reduction in the intake of 1% sucrose (anhedonia), as well as attenuated adrenocorticotropic hormone (ACTH) responses to 8-OH-DPAT in both male and female rats (22 and 18% lower than the control groups, respectively). Corticosterone and oxytocin responses to 8-OH-DPAT were not altered by exposure to CMS. In female rats, CMS induced a lengthening of the estrous cycle by similar to 40%. CMS produces minor HPA disruptions along with behavioral disruptions. Alterations in 5-HT1A receptor function in specific populations of neurons in the central nervous system may be associated with the CMS model. The current findings contribute to our understanding of the relations that stress and neuroendocrine function have to depressive disorders.