Overexpression of proenkephalin in the amygdala potentiates the anxiolytic effects of benzodiazepines
Overexpression of proenkephalin in the amygdala potentiates the anxiolytic effects of benzodiazepines
复制标题
DOI：
10.1016/s0893-133x(99)00090-1
复制
发表时间：
2000-01-01
影响因子：
7.6
通讯作者：
Wilson, MA
中科院分区：
文献类型：
--
作者：
Kang, W;Wilson, SP;Wilson, MA
为了阐明阿片肽在控制苯二氮卓类药物的焦虑样行为和减轻焦虑作用中的作用，我们将携带人前脑啡肽cDNA的重组复制缺陷性疱疹病毒（SHPE）传递到大鼠杏仁核。病毒感染后2-4天产生强烈的、局部的转基因表达，一周后转基因表达减弱。在基因传递3天后，采用升高+迷宫试验评估类焦虑行为和安定的抗焦虑作用。虽然SHPE感染本身并不能减少焦虑样行为，但与感染含有lacZ基因的对照病毒（shz - 1）的大鼠相比，感染SHPE的大鼠对安定的抗焦虑作用表现出更大的反应。SHPE对地西泮作用的增强是纳洛酮可逆的，具有区域特异性，并与脑啡肽前原表达的时间过程相关。研究结果提示杏仁核阿片肽参与调节苯二氮卓类药物的抗焦虑作用。该研究还证明了重组疱疹病毒在评估特定脑部位的单基因产物在药理反应和复杂行为中的作用方面的有效性。[j] .中华医学会精神病学分会，2002。Elsevier Science Inc.出版。
To elucidate the role of opioid peptides in control of the anxiety-like behavior and anxiety-reducing actions of benzodiazepines a recombinant, replication-defective herpes virus (SHPE) carrying human preproenkephalin cDNA was delivered to rat amygdala. viral infection resulted in a strong, localized transgene expression after 2-4 days which diminished after one week. Anxiety-like behavior and the anxiolytic effect of diazepam were assessed three days after gene delivery using the elevated plus maze test. While SHPE infection alone did not reduce anxiety-like behavior, rats infected with SHPE exhibited a greater response to the anxiolytic effect of diazepam when compared to rats infected with a control virus (SHZ.1) containing the lacZ gene. The enhancement of diazepam action by SHPE was naloxone reversible, region-specific, and correlated with the time course of preproenkephalin expression. The findings implicate amygdalar opioid peptides in regulating the anxiolytic effects of benzodiazepines. This study also demonstrates the usefulness of recombinant herpes virus in evaluating the role of single gene products within specific brain sites in pharmacological responses and complex behaviors. [Neuropsychopharmacology 22:77-88, 2000] (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.