THE ANTERIOR CINGULATE CORTEX IS A TARGET STRUCTURE FOR THE ANXIOLYTIC-LIKE EFFECTS OF BENZODIAZEPINES ASSESSED BY REPEATED EXPOSURE TO THE ELEVATED PLUS MAZE AND FOS IMMUNOREACTIVITY
THE ANTERIOR CINGULATE CORTEX IS A TARGET STRUCTURE FOR THE ANXIOLYTIC-LIKE EFFECTS OF BENZODIAZEPINES ASSESSED BY REPEATED EXPOSURE TO THE ELEVATED PLUS MAZE AND FOS IMMUNOREACTIVITY
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DOI：
10.1016/j.neuroscience.2009.08.038
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发表时间：
2009-12-01
期刊：
影响因子：
3.3
通讯作者：
Brandao, M. L.
中科院分区：
文献类型：
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作者：
Albrechet-Souza, L.;Borelli, K. G.;Brandao, M. L.
先前使用高架十字迷宫（EPM）的经验会增加啮齿动物对张开双臂的回避，并削弱苯二氮卓类药物对重新暴露于迷宫时评估的传统行为的抗焦虑样作用，这种现象称为单次试验耐受性。风险评估行为对苯二氮卓类药物也很敏感。在重新暴露于迷宫的过程中，这些行为会恢复第一次体验期间启动的信息处理，并且对危险的检测会产生更强烈的张开手臂回避。本研究调查了苯二氮卓类咪达唑仑是否会改变与 EPM 中的测试和重新测试相关的风险评估行为和 Fos 蛋白分布。初次或经历过迷宫的 Wistar 大鼠接受盐水或咪达唑仑（0.5 mg/kg i.p.）并接受 EPM。咪达唑仑对探索行为产生了常见的影响，增加了张开双臂的幼稚大鼠的探索活动，而对重新暴露于迷宫的大鼠的这些常规措施没有产生影响。然而，在这两个疗程中，风险评估行为对苯二氮卓类药物都很敏感，表明该药物在这两种情况下都具有抗焦虑样作用。 Fos 免疫组织化学显示，在测试或重新测试之前注射咪达唑仑时，注射会产生不同的作用模式，并且前扣带皮层 1 区 (Cg1) 是这两种情况下苯二氮卓类药物唯一靶向的结构。双侧注射咪达唑仑至 Cg1 复制了全身注射药物的行为效应，表明该区域与苯二氮卓类药物的抗焦虑样作用密切相关，尽管动物采用的行为策略似乎取决于先前对威胁环境的了解。 (C) 2009 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Prior experience with the elevated plus maze (EPM) increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effects of benzodiazepines on the traditional behaviors evaluated upon re-exposure to the maze, a phenomenon known as one-trial tolerance. Risk assessment behaviors are also sensitive to benzodiazepines. During re-exposure to the maze, these behaviors reinstate the information-processing initiated during the first experience, and the detection of danger generates stronger open-arm avoidance. The present study investigated whether the benzodiazepine midazolam alters risk assessment behaviors and Fos protein distribution associated with test and retest sessions in the EPM. Naive or maze-experienced Wistar rats received either saline or midazolam (0.5 mg/kg i.p.) and were subjected to the EPM. Midazolam caused the usual effects on exploratory behavior, increasing exploratory activity of naive rats in the open arms and producing no effects on these conventional measures in rats re-exposed to the maze. Risk assessment behaviors, however, were sensitive to the benzodiazepine during both sessions, indicating anxiolytic-like effects of the drug in both conditions. Fos immunohistochemistry showed that midazolam injections were associated with a distinct pattern of action when administered before the test or retest session, and the anterior cingulate cortex, area 1 (Cg1), was the only structure targeted by the benzodiazepine in both situations. Bilateral infusions of midazolam into the Cg1 replicated the behavioral effects of the drug injected systemically, suggesting that this area is critically involved in the anxiolytic-like effects of benzodiazepines, although the behavioral strategy adopted by the animals appears to depend on the previous knowledge of the threatening environment. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.