The amygdaloid 5-HT2C receptor in anxiety-like behavior

杏仁核5-HT2C受体在焦虑样行为中的作用

• 批准号: 7140509
• 负责人: QIAN LI
• 金额: $ 14.75万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140509
• 关键词: Adenoviridae; amygdala; anxiety; anxiety disorders; behavior test; behavioral /social science research tag; conditioning; disease /disorder etiology; ethology; fear; laboratory mouse; neuropsychology; neuroregulation; open field behavior; protein localization; receptor expression; recombinant virus; serotonin receptor; stereotaxic techniques; Adenoviridae; amygdala; anxiety; anxiety disorders; behavior test; behavioral /social science research tag; conditioning; disease /disorder etiology; ethology; fear; laboratory mouse; neuropsychology; neuroregulation; open field behavior; protein localization; receptor expression; recombinant virus; serotonin receptor; stereotaxic techniques

DESCRIPTION (provided by applicant): Anxiety disorder is one of the most common mental health problems in the United States. It also accompanies with other affective disorders such as depression. The etiology for anxiety disorders is still unknown and may be complicated. Furthermore, current therapeutic approaches suffer from serious deficiencies. Therefore, it is essential to study the etiology of anxiety disorders and develop better therapeutic approaches for anxiety disorders. Serotonin2c (5- HT2c) receptors play a role in the regulation of anxiety behaviors. Studies, from both humans and rodents, indicate that activation of 5-HT2c receptors produces an anxiogenic effect. Increased sensitivity of 5-HT2c receptors was found in patients with panic disorder. Conversely, 5-HT2c receptor antagonists produce anxiolytic effect. However, little is known regarding the neural circuitry and the cellular and molecular mechanisms that mediate the effect of 5-HT2c receptors on the regulation of anxiety behaviors. The objective of the current application is to determine the role of amygdaloid 5-HT2c receptors in the regulation of anxiety-like behaviors. Our hypothesis is that 5-HT2c receptors in the amygdala play an important role in the regulation of anxiety-like behaviors. The amygdala is known as a fear center and it contains a high density of 5-HT2c receptors. We recently found that serotonin transporter knockout mice show increased anxiety-like behaviors and that the density of 5-HT2c receptors is increased in the amygdala of these mice. To test the hypothesis, we will pursue 2 specific aims: 1) We will characterize recombinant adenovirus containing 5-HT2c sense and antisense sequences, so that they can be used to manipulate the expression of 5-HT2c receptors; and 2) We will determine the effect of 5-HT2c receptors in the amygdala on anxiety-like behaviors. Anxiety like behavior of the animals will be assessed by elevated plus maze, open field and fear conditioning tests. The outcome of the studies will be the first line of evidence for the location of 5-HT2c receptors that are involved in the regulation of anxiety behavior, which will be the foundation for the future studies on the neuronal circuitries and the cellular and molecular mechanisms mediating 5-HT2c receptor-involved regulation of anxiety behaviors. Furthermore, the proposed studies have a high potential of leading to the development of novel drugs to treat anxiety disorders.

描述（由申请人提供）：焦虑症是美国最常见的心理健康问题之一。它还伴随着其他情感障碍，例如抑郁症。焦虑症的病因仍然未知，可能很复杂。此外，当前的治疗方法严重缺陷。因此，研究焦虑症的病因并为焦虑症开发更好的治疗方法至关重要。血清素2c（5- HT2C）受体在调节焦虑行为中起作用。来自人类和啮齿动物的研究表明，5-HT2C受体的激活产生焦虑作用。在恐慌症患者中发现5-HT2C受体的敏感性提高。相反，5-HT2C受体拮抗剂产生抗焦虑作用。然而，关于介导5-HT2C受体对调节焦虑行为的影响的神经回路以及细胞和分子机制知之甚少。当前应用的目的是确定杏仁核5-HT2C受体在调节焦虑样行为中的作用。我们的假设是，杏仁核中的5-HT2C受体在调节焦虑样行为中起着重要作用。杏仁核被称为恐惧中心，其中含有高密度的5-HT2C受体。我们最近发现，5-羟色胺转运蛋白敲除小鼠表现出增加的焦虑样行为，并且这些小鼠的杏仁核中5-HT2C受体的密度增加。为了检验假设，我们将追求2个具体目的：1）我们将表征包含5-HT2C感觉和反义序列的重组腺病毒，以便它们可以用来操纵5-HT2C受体的表达； 2）我们将确定5-HT2C受体在杏仁核中对焦虑样行为的影响。像动物的焦虑一样，将通过升高的迷宫，开放式和恐惧调节测试来评估。研究的结果将是参与调节焦虑行为的5-HT2C受体位置的第一条证据，这将是对神经元循环的未来研究以及介导5-HT2C受体受体调节焦虑行为调节的未来研究的基础。此外，拟议的研究具有导致新药治疗焦虑症的新药物的高潜力。