束缚应激对 Wistar-Kyoto 大鼠和 Brown Norway 大鼠的前脉冲抑制和促肾上腺皮质释放因子 (CRF)及 CRF 受体基因表达的影响。
The effect of restraint stress on prepulse inhibition and on corticotropin-releasing factor (CRF) and CRF receptor gene expression in Wistar-Kyoto and Brown Norway rats.
机构信息
Department of Psychiatry, University of Connecticut Health Center, Farmington, CT 06030, USA.
出版信息
Pharmacol Biochem Behav. 2010 Dec;97(2):227-38. doi: 10.1016/j.pbb.2010.08.003. Epub 2010 Aug 13.
Stress plays a role in many psychiatric disorders that are characterized by deficits in prepulse inhibition (PPI), a form of sensorimotor gating. Corticotropin-releasing factor (CRF) is one of the most important neurotransmitters involved in behavioral components of the stress response, and central infusion of CRF decreases PPI in rodents. We recently demonstrated that restraint stress decreases PPI and attenuates the increase in PPI caused by repeated testing. To broaden our investigation into how restraint affects PPI, we subjected Wistar-Kyoto (WKY) and Brown Norway (BN) rats to 10 consecutive days of 2-hour restraint, or to brief handling, prior to assessing PPI. We next examined the effects of 1 or 10days of 2-hour restraint on plasma corticosterone levels in order to determine whether the endocrine response to stress parallels the behavioral effect of stress. Finally, we examined the effects of 1 or 10days of 2-hour restraint on CRF and CRF receptor gene expression in the amygdala, hippocampus, frontal cortex, and hypothalamus in order to determine whether a temporal pattern of gene expression parallels the change in the behavioral response to stress. The major findings of the present study are that 1) restraint stress attenuates the increase in PPI caused by repeated testing in both WKY and BN rats, and BN rats are more sensitive to the effects of restraint on PPI than WKY rats, 2) restraint-induced increases in corticosterone levels mirror the effect of restraint on PPI in WKY rats but not in BN rats, 3) laterality effects on gene expression were observed for the amygdala, whereby restraint increases CRF gene expression in the left, but not right, amygdala, and 4) some restraint-induced changes in CRF and CRF receptor gene expression precede changes in PPI while other changes coincide with altered PPI in a rat strain- and brain region-dependent manner.
压力在许多以预脉冲抑制（PPI）缺陷为特征的精神疾病中起作用，PPI 是一种感觉运动门控形式。促肾上腺皮质释放因子（CRF）是参与应激反应行为成分的最重要神经递质之一，而 CRF 的中枢输注可降低啮齿动物的 PPI。我们最近证明，束缚应激会降低 PPI 并减弱重复测试引起的 PPI 增加。为了更广泛地研究束缚如何影响 PPI，我们让 Wistar-Kyoto（WKY）和 Brown Norway（BN）大鼠连续 10 天接受 2 小时的束缚，或进行短暂的处理，然后评估 PPI。接下来，我们检查了 1 或 10 天 2 小时束缚对血浆皮质酮水平的影响，以确定应激的内分泌反应是否与应激的行为效应平行。最后，我们检查了 1 或 10 天 2 小时束缚对杏仁核、海马、前额叶皮层和下丘脑的 CRF 和 CRF 受体基因表达的影响，以确定基因表达的时间模式是否与应激对行为反应的变化平行。本研究的主要发现是：1）束缚应激减弱了 WKY 和 BN 大鼠重复测试引起的 PPI 增加，并且 BN 大鼠对束缚对 PPI 的影响比 WKY 大鼠更敏感，2）束缚引起的皮质酮水平升高反映了束缚对 WKY 大鼠 PPI 的影响，但对 BN 大鼠没有影响，3）在杏仁核中观察到基因表达的偏侧性效应，即束缚增加了左侧而非右侧杏仁核的 CRF 基因表达，以及 4）一些 CRF 和 CRF 受体基因表达的束缚诱导变化先于 PPI 的变化，而其他变化则与改变的 PPI 同时发生，这取决于大鼠的品种和大脑区域。
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