NEUROBIOLOGY OF PANIC AND ANXIETY DISORDERS

描述（改编自申请人的摘要）：惊恐障碍是一种严重的 一种以反复发作的恐慌为特征的焦虑症， 占人口的2%。 神经生物学机制参与的 对恐慌症的发展知之甚少。 远程 目的是为了更清楚地了解 严重焦虑状态和惊恐发作的神经回路 本研究的目的是描述 产生恐慌症的神经回路 的 有待检验的假设是，在神经元中存在慢性不平衡， 下丘脑背内侧（DMH）的功能， 制造恐慌症。 这种不平衡可能是由于 紧张性抑制作用的减少，兴奋性 功能或两者的组合。 这一假设将在大鼠中进行检验 在DMH中实验诱导的GABA功能障碍中。 具体 目的是确定：1）时间过程，解剖特异性 慢性DMH GABA动物的药理学特征 兴奋性氨基酸神经传递的相互作用 慢性GABA功能障碍大鼠DMH内GABA的含量; DMH中GABA功能障碍对细胞外 去甲肾上腺素（NE）在这个区域和之间的潜在电路 DMH和蓝斑; 4）室周核受累 终板血管器（OVLT） DMH中GABA功能障碍引起的恐慌样反应。 行为 焦虑的措施将与社会互动和提高 十字迷宫测试 测量心率、血压和呼吸 速率将用于评估由i. v. 乳酸盐输注。 立体定位程序将用于a）特定部位 用Alzet微型泵进行微量输注以产生慢性GABA功能障碍， 进行药理学研究和B）用于植入微透析 probes. HPLC-EC程序将用于测量GABA组织水平， 细胞外NE浓度。 这项研究的结果将 希望能增强我们对恐慌的神经生物学的理解 disorder.

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.