Involvement of the midbrain tectum in the unconditioned fear promoted by morphine withdrawal
Involvement of the midbrain tectum in the unconditioned fear promoted by morphine withdrawal
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DOI：
10.1016/j.ejphar.2008.06.030
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发表时间：
2008-08-20
影响因子：
5
通讯作者：
Castilho, Vanessa M.
中科院分区：
文献类型：
--
作者：
Avila, Milton A. V.;Ruggiero, Rafael N.;Castilho, Vanessa M.
中脑直肠结构，背中脑导水管周围灰质(DPAG)和下丘(IC)，在暴露于危险刺激时参与组织恐惧和焦虑状态。由于阿片类药物戒断与人类和动物的焦虑增加有关，本研究旨在研究中脑顶盖恐惧神经底物的可能敏化及其对吗啡戒断诱导的焦虑的影响。为了产生药物戒断，大鼠接受了吗啡注射(10 mg/kg；S.C.)在10天内每天两次。在慢性治疗中断48小时后，在高架正迷宫和开场测试中对独立组进行探测。另将双极电极植入IC的DPAG内，电刺激这些结构，测定停药48h后的冰冻阈值和逃逸阈值。我们的结果显示，吗啡戒断促进了明显的焦虑水平，而没有阿片类药物戒断的躯体迹象。此外，吗啡戒断大鼠对电刺激DPAG和IC的反应性增加。这些发现表明，吗啡戒断引起的焦虑增加与DPAG和IC中恐惧神经底物的敏化有关。因此，本研究结果支持戒断吗啡慢性治疗会导致恐惧状态的假说，这种恐惧状态可能是通过激活DPAG和IC而产生的，而与躯体症状的产生无关。(C)2008爱思唯尔B.V.保留所有权利。
The midbrain rectum structures, dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), are involved in the organization of fear and anxiety states during the exposure to dangerous stimuli. Since opiate withdrawal is associated with increased anxiety in both humans and animals, this study aimed to investigate the possible sensitization of the neural substrates of fear in the midbrain tectum and its influence on the morphine withdrawal-induced anxiety. For the production of drug withdrawal, rats received morphine injections (10 mg/kg; s.c.) twice daily during 10 days. Forty-eight hours after the interruption of the chronic treatment, independent groups were probed in the elevated plus-maze and open-field tests. Additional groups of animals were implanted with a bipolar electrode into the dPAG OF the IC and submitted to the electrical stimulation of these structures for the determination of the freezing and escape thresholds after 48 h of withdrawal. Our results showed that the morphine withdrawal promoted clear-cut levels of anxiety without the somatic signs of opiate withdrawal. Moreover, morphine-withdrawn rats had an increase in the reactivity to the electrical stimulation of the dPAG and the IC. These findings suggest that the increased anxiety induced by morphine withdrawal is associated with the sensitization of the neural substrates of fear in the dPAG and the IC. So, the present results give support to the hypothesis that withdrawal from chronic treatment with morphine leads to fear states possibly engendered by activation of the dPAG and IC, regardless of the production of somatic symptoms. (C) 2008 Elsevier B.V. All rights reserved.