Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress
Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress
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DOI：
10.1016/j.bbr.2007.02.001
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发表时间：
2007-05-16
影响因子：
2.7
通讯作者：
Pearcey, K.
中科院分区：
文献类型：
--
作者：
Adamec, R.;Muir, C.;Pearcey, K.
研究了β-NER（β-去甲肾上腺素能受体）、GR（糖皮质激素）和矿物质皮质激素受体（MR）在捕食者应激致焦虑效应巩固中的作用。捕食者应激后1分钟，向不同组大鼠注射（ip）赋形剂、普萘洛尔（β-NER阻滞剂，5和10 mg/kg）、米非司酮（RU 486，GR阻滞剂，20 mg/kg）、螺内酯（MR阻滞剂，50 mg/kg）、普萘洛尔（5 mg/kg）加RU 486（20 mg/kg）或抗焦虑药、氯氮环氧化物（CPZ，10 mg/kg）。一周后，在高架十字迷宫、孔板、光/暗盒、社会互动和声惊吓中评估啮齿动物的焦虑。考虑到所有的测试，除了惊吓，普萘洛尔剂量依赖性地阻止巩固持久的焦虑作用的捕食者压力在所有的测试。单独GR受体阻断无效。然而，GR块结合无效剂量的普萘洛尔确实阻止巩固的捕食者压力的影响，在所有的测试中，这表明β-NER和GR之间的协同作用。令人惊讶的是，MR块防止巩固的焦虑作用，在所有的测试中，除了光/黑盒子。CPZ后应激对捕食者应激的焦虑影响无效。应激对惊吓幅度的焦虑效应表现为惊吓幅度的增加和减少，这一事实使惊吓的研究变得复杂。抑制惊吓发生在强调加上车辆注射组处理前三次捕食者压力。相比之下，强调加上车辆大鼠处理五次之前，捕食者的压力表现出增加惊吓，因为所有捕食者强调只组。不同惊吓反应的巩固机制似乎不同。CPZ后应激阻断惊吓抑制，但不增强惊吓。普萘洛尔应激后对惊吓的抑制或增强均无影响。应激后单独GR阻滞可抑制惊吓，但不能增强。相反，阻断GR和β-NER一起防止惊吓增强。MR阻滞也可防止惊吓增强。没有测试MR阻断对惊吓抑制的影响。所有应激大鼠对惊吓的适应延迟。应激后MR阻滞、GR + β-NER阻滞和CPZ均能阻断或减弱习惯化延迟的巩固，但应激后GR或β-NER单独阻滞则不能。两者合计，目前的研究结果表明，巩固持久的焦虑的影响，捕食者的压力可能会分享一些相同的神经化学机制，牵连在某些形式的恐惧记忆巩固。这些研究结果的影响，包括创伤后应激障碍（PTSD）的研究压力引起的变化进行了讨论。(c)2007 Elsevier B. V.保留所有权利。
The roles of beta-NER (beta-noradrenergic receptor), GR (glucocorticoid) and mineral corticoid receptors (MR) in the consolidation of anxiogenic effects of predator stress were studied. One minute after predator stress, different groups of rats were injected (ip) with vehicle, propranolol (beta-NER blocker, 5 and 10 mg/kg), mifepristone (RU486, GR blocker, 20 mg/kg), spironolactone (MR blocker, 50 mg/kg), propranolol (5 mg/kg) plus RU486 (20 mg/kg) or the anxiolytic, chloradiazepoxide, (CPZ, 10 mg/kg). One week later, rodent anxiety was assessed in elevated plus maze, hole board, light/dark box, social interaction and acoustic startle. Considering all tests except startle, propranolol dose dependently blocked consolidation of lasting anxiogenic effects of predator stress in all tests. GR receptor block alone was ineffective. However, GR block in combination with an ineffective dose of propranolol did blocked consolidation of predator stress effects in all tests, suggesting a synergism between beta-NER and GR. Surprisingly, MR block prevented consolidation of anxiogenic effects in all tests except the light/dark box. CPZ post stress was ineffective against the anxiogenic impact of predator stress. Study of startle was complicated by the fact that anxiogenic effects of stress on startle amplitude manifested as both an increase and a decrease in startle amplitude. Suppression of startle occurred in stressed plus vehicle injected groups handled three times prior to predator stress. In contrast, stressed plus vehicle rats handled five times prior to predator stress showed increases in startle, as did all predator stressed only groups. Mechanisms of consolidation of the different startle responses appear to differ. CPZ post stress blocked startle suppression but not enhancement of startle. Propranolol post stress had no effect on either suppression or enhancement of startle. GR block alone post stress prevented suppression of startle, but not enhancement. In contrast blocking GR and beta-NER together prevented startle enhancement. MR block also prevented startle enhancement. Effects of MR block on startle suppression were not tested. Delay of habituation to startle was found in all stressed rats. Consolidation of delay of habituation was blocked or attenuated by post stress MR block, GR plus beta-NER block and CPZ but not by post stress GR or beta-NER block alone. Taken together, present findings suggest consolidation of lasting anxiogenic effects of predator stress may share some of the same neurochemical mechanisms implicated in some forms of fear memory consolidation. Implications of these findings for the study of stress-induced changes in affect including posttraumatic stress disorder (PTSD) are discussed. (c) 2007 Elsevier B.V. All rights reserved.