Amygdalar neuropeptides and anxiety

杏仁核神经肽和焦虑

• 批准号: 6944356
• 负责人: Marlene A. Wilson
• 金额: $ 25.46万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6944356
• 关键词: Alphaherpesvirinae; amygdala; anxiety; anxiety disorders; behavior test; benzodiazepines; biological models; biotechnology; buspirone; enkephalins; ethanol; fear; gene expression; genetically modified animals; immunocytochemistry; laboratory rat; neuropeptides; neuropharmacology; opioid receptor; psychopharmacology; radioimmunoassay; tranquilizer; transfection; transfection /expression vector

DESCRIPTION (provided by applicant): The amygdala is a brain structure that plays a crucial role in fear and anxiety, and the actions of anxiety-reducing compounds. The opioid peptide has also been shown to modulate anxiety-related responses within the amygdala. Using herpes virus-mediated gene transfer, we have demonstrated that overexpression of enkephalin in the amygdala enhances the anxiety-reducing influences of the benzodiazepine diazepam (Valium) in rats. These initial results demonstrate that herpes virus-mediated gene transfer can transiently alter expression of neuropeptides in confined brain sites of adult rats, and that these changes can modify behavioral responses. The present studies continue to utilize this powerful technique to examine the role of amygdalar enkephalin in regulating anxiety-related behaviors and the actions of anxiolytic drugs. Both decreases and cell-targeted increases in peptide expression will be examined in several animal models of anxiety. Aim 1 will verify the ability of virus-mediated gene transfer to decrease and cell-specifically increase expression of enkephalin in select areas of amygdala. Anatomical and quantitative methods will assess changes in mRNA expression, while peptide changes will be assessed with immunohistochemistry and radioimmunoassay. AIM 2 examines if altered enkephalin expression in central amygdala modifies anxiety-related behaviors in additional animal tests of anxiety behaviors and/or the effectiveness of other anxiolytics in these tests. These studies 1) compare decreases with cell-specific increases in enkephalin expression, 2) test the activity of other anxiolytics (alcohol, the serotonergic compound buspirone), and 3) tests effects in several models of anxiety. AIM 3 assesses the effects of pharmacological modulation of enkephalin activity in amygdala. Using more traditional techniques selective opioid receptor (mu, delta) agonists and antagonists will be locally applied in amygdala, and the effect of these compounds on responses to anxiolytic drugs will be tested. These studies will lead to a better understanding of the role of amygdala and enkephalin in anxiety and anxiolytic responses, as well as elucidate the differences between animal models of anxiety. This understanding may also suggest novel, avenues for development of treatments for anxiety or affective disorders.

描述（由申请人提供）：杏仁核是一种大脑结构，在恐惧和焦虑中起着至关重要的作用，以及减轻焦虑的化合物的作用。阿片类肽也已显示可调节杏仁核内与焦虑相关的反应。使用疱疹病毒介导的基因转移，我们已经证明，杏仁核中的eNkephalin过表达可以增强大鼠苯二氮卓氮杂地西ep（valium）的焦虑减轻影响。这些最初的结果表明，疱疹病毒介导的基因转移可以瞬时改变成年大鼠狭窄的大脑部位的神经肽的表达，并且这些变化可以改变行为反应。本研究继续利用这种强大的技术来检查杏仁核烯基链林在调节焦虑相关行为和抗焦虑药的作用中的作用。在几种焦虑动物模型中将检查肽表达的降低和细胞靶向的增加。 AIM 1将验证病毒介导的基因转移的能力降低和细胞特异性增加Enkephalin在杏仁核的选择区域的表达。解剖学和定量方法将评估mRNA表达的变化，而肽变化将通过免疫组织化学和放射免疫分析进行评估。 AIM 2检查中央杏仁核中的Enkephalin表达是否改变会在焦虑行为的其他动物测试和/或其他焦虑症在这些测试中的有效性中修饰与焦虑相关的行为。这些研究1）比较Enkephalin表达的细胞特异性降低，2）测试其他抗焦虑药的活性（酒精，血清素能化合物丁螺旋酮）和3）在几种焦虑模型中的测试影响。 AIM 3评估了杏仁核中Enkephalin活性的药理调节的影响。使用更传统的技术选择性阿片受体（MU，Delta）激动剂和拮抗剂将在杏仁核中局部应用，这些化合物对抗焦虑药的反应的影响将进行测试。这些研究将使人们更好地了解杏仁核和恩基法林在焦虑和抗焦虑反应中的作用，并阐明焦虑动物模型之间的差异。这种理解也可能暗示了新颖的焦虑或情感障碍治疗方法的途径。