NEUROBIOLOGY OF PANIC AND ANXIETY DISORDERS

恐慌和焦虑症的神经生物学

• 批准号: 2675224
• 负责人: Anantha Shekhar
• 金额: $ 13.22万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2675224
• 关键词: anxiety; anxiety disorders; behavior test; disease /disorder model; drug delivery systems; excitatory aminoacid; gamma aminobutyrate; high performance liquid chromatography; hypothalamus; intravenous administration; laboratory rat; lactates; locus coeruleus; microinjections; neural transmission; neuroanatomy; neurobiology; neurochemistry; neuroendocrine system; norepinephrine; panic disorder; psychopharmacology; stereotaxic techniques

DESCRIPTION (Adapted from applicant's abstract): Panic disorder is a severe anxiety disorder characterized by recurrent panic attacks affecting about 1 to 2% of the population. The neurobiological mechanisms involved in the development of panic attacks are poorly understood. The long range objectives are to provide a clearer understanding of the abnormalities in the neuronal circuits underlying severe anxiety states and panic attacks. The objective of the present study is to characterize the abnormalities in the neural circuits underlying the production of panic attacks. The hypothesis to be tested is that there is a chronic imbalance in the neuronal function within the dorsomedial hypothalamus (DMH) which underlies the production of panic attacks. This imbalance could be a result of a net reduction in a tonic inhibitory influence, a net increase in excitatory function, or combination of both. This hypothesis will be tested in rats within experimentally induced GABA dysfunction in the DMH. The specific aims are designed to determine: 1) the time course, anatomical specificity and pharmacological profile of the animals with chronic DMH GABA dysfunction; 2) the interaction of excitatory amino acid neurotransmission and GABA within the DMH in rats with chronic GABA dysfunction; 3) the effects of GABA dysfunction in the DMH on the extracellular levels of norepinephrine (NE) in this region and the potential circuits between the DMH and the locus ceruleus; 4) the involvement of the circumventricular organ, organum vasculosum lamina terminalis (OVLT) in the lactate induced panic-like responses elicited by GABA dysfunction in the DMH. Behavioral measures of anxiety will be undertaken with social interaction and elevated plus-maze tests. Measurements of heart rate, blood pressure and respiratory rate will be used to assess the onset of a panic attack induced by i.v. lactate infusions. Stereotaxic procedures will be used a) for site specific microinfusions to produce chronic GABA dysfunction with Alzet minipumps and to undertake pharmacological studies and b) for implanting microdialysis probes. HPLC-EC procedures will be used to measure GABA tissue levels and extracellular concentrations of NE. The results of this study will hopefully enhance our current understanding of the neurobiology of panic disorder.

描述(摘自申请者的摘要)：惊恐障碍是一种严重的 焦虑症的特征是反复发作的恐慌性发作，影响约1 到2%的人口。神经生物学机制涉及到的 人们对恐慌症发作的发展情况知之甚少。长距离的 目的是为了让人们更清楚地了解 严重焦虑状态和恐慌症发作背后的神经元回路。 本研究的目的是描述这些异常的特征。 导致恐慌症发作的神经回路。这个 有待检验的假设是，神经元中存在慢性不平衡 背内侧下丘脑(DMH)内的功能 恐慌性发作的产生。这种不平衡可能是净值的结果 紧张性抑制影响减少，兴奋性净增加 功能，或两者的组合。这一假说将在大鼠身上进行检验。 在实验中诱导DMH中的GABA功能障碍。具体的 目的是确定：1)时间进程、解剖特异度 慢性DMH-GABA动物模型的药理作用 2)兴奋性氨基酸类神经递质的相互作用 慢性GABA功能障碍大鼠DMH内GABA和GABA的变化 DMH中GABA功能障碍对细胞外钙离子水平的影响 去甲肾上腺素(NE)在这一区域的作用 DMH和蓝斑；4)累及脑室周围 乳酸诱导的终板血管器官(OVLT) DMH中GABA功能障碍引起的恐慌样反应。行为 焦虑的测量将通过社交互动进行，并提高 加迷宫测试。测量心率、血压和呼吸 Rate将被用来评估静脉注射引起的恐慌症发作的开始。 乳酸输液。立体定位程序将用于a)特定的站点 微量输注导致阿尔茨海默病患者慢性GABA功能障碍 进行药理研究和b)植入微透析 探测器。高效液相色谱-电化学法将被用来测量GABA组织水平和 去甲肾上腺素胞外浓度。这项研究的结果将 希望能加强我们目前对恐慌的神经生物学的理解 无序。