Chronic morphine selectively impairs cued fear extinction in rats: Implications for anxiety disorders associated with opiate use
Chronic morphine selectively impairs cued fear extinction in rats: Implications for anxiety disorders associated with opiate use
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DOI：
10.1038/sj.npp.1301441
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发表时间：
2008-02-01
影响因子：
7.6
通讯作者：
Hu, Xintian
中科院分区：
文献类型：
--
作者：
Gu, Chaoliang;Li, Peng;Hu, Xintian
以往的研究表明，阿片传递在学习和记忆中起着重要作用。然而，在行为动物模型中，停止慢性阿片类药物使用后，阿片类药物相关的学习和记忆缺陷的过程知之甚少。在本研究中，我们研究了慢性吗啡对恐惧消退的影响，恐惧消退是人类焦虑障碍行为治疗的重要临床前模型。大鼠分别皮下注射盐酸吗啡或生理盐水，每天2次，连续10天。大鼠在最后一次注射吗啡后7天接受提示或情境恐惧条件反射。在随后的几天里，大鼠接受了四次暗示或情境灭绝训练（每天一次）。在训练的所有阶段评估冻结的百分比。慢性吗啡不影响提示恐惧反应的习得和消退记忆的初始编码，但会对间歇消退产生损害。然而，相同的吗啡治疗方案不影响情境恐惧反应的获得或消失。这些结果表明，慢性吗啡对恐惧消退记忆的影响是复杂的。慢性吗啡选择性地损害暗示恐惧反应的消退。这种恐惧消除的缺陷可能是导致阿片类成瘾者中焦虑症高发的关键因素之一。
Previous studies have shown that opioid transmission plays an important role in learning and memory. However, little is known about the course of opiate-associated learning and memory deficits after cessation of chronic opiate use in a behavioral animal model. In the present study, we examined the effects of chronic morphine on fear extinction, an important preclinical model for behavior therapy of human anxiety disorders. Rats were administrated subcutaneously morphine hydrochloride or saline twice per day for continuous 10 days. Rats received a cued or contextual fear conditioning session 7 days after the last morphine injection. During subsequent days, rats received four cued or contextual extinction sessions ( one session per day). Percent freezing was assessed during all phases of training. Chronic morphine did not affect the acquisition of cued fear response or the initial encoding of extinction memory within each session, but produced an impairment in the between-session extinction. However, the same morphine treatment schedule did not affect the acquisition or extinction of contextual fear response. These results suggest that the effects of chronic morphine on memory for fear extinction are complex. Chronic morphine selectively impairs extinction of cued fear response. This deficit in fear extinction may be one of those critical components that contribute to the high prevalence of anxiety disorders in opiate addicts.