PSYCHOPHYSIOLOGY AND ANXIOGENESIS

描述（申请人摘要）：本竞争性研究中提出的研究 更新申请将检查基底前脑皮层的作用， 胆碱能系统在行为和心血管功能的恐惧和 焦虑该研究由两个假设指导：a）喙 恐惧和焦虑背后的神经行为机制可以调节自主神经功能， 控制，和B）病理介导的内脏反应可以调节 通过中枢上行通路的焦虑相关背景的皮层处理。 后者包括基底前脑皮质胆碱能投射， 与恐惧相关的心血管反应有关， 焦虑拟议的工作将进一步开发和测试神经生物学 恐惧和焦虑的中枢系统模型。具体重点是 基底前脑胆碱能系统及其在行为整合中的作用 和心血管反应。这项工作将确定相关的目标地点， 中枢注射阿托伐他汀对大鼠基底前脑胆碱能系统的影响 胆碱能特异性免疫毒素（192 IgG-皂草素），以及胆碱能和 肾上腺素能药物和苯二氮卓受体激动剂、拮抗剂和反 激动剂其他拟议中的研究将阐明 它的基底前脑胆碱能系统是有效的， 关于模型的上升分量的假设。这些包括 检查内脏传入在调节行为和 在焦虑背景下的自主反应，通过皮下注射 迷走神经切断术和其他方法。拟议的研究涉及基本的 焦虑的本质和潜在的神经机制， 过程和自主功能。这些都是重要的问题， 焦虑症的患病率，以及抗焦虑药苯二氮卓类药物 受体激动剂是最广泛使用的精神药物 国际吧因为焦虑症通常与异常的 自主调节，它们代表心血管疾病的明显危险因素 疾病和心脏猝死。

DESCRIPTION (applicant's abstract): The research proposed in this competitive renewal application would examine the role of the basal forebrain cortical cholinergic system in behavioral and cardiovascular features of fear and anxiety. The research is guided by two hypotheses: a) that rostral neurobehavioral mechanisms underlying fear and anxiety can modulate autonomic control, and b) that autonomically mediated visceral reactions can modulate the cortical processing of anxiety-related contexts via central ascending pathways. The latter includes the basal forebrain cortical cholinergic projection, which has been implicated in cardiovascular reactivity associated with fear and anxiety. The proposed work will further develop and test a neurobiological model of central systems underlying fear and anxiety. Specific emphasis is on the basal forebrain cholinergic system and its role in integrating behavioral and cardiovascular reactions. The work will identify relevant target sites of the basal forebrain cholinergic system in rats, by central infusions of a cholinergic-specific immunotoxin (192IgG-saporin), as well as cholinergic and adrenergic drugs and benzodiazepine receptor agonists, antagonists, and inverse agonists. Other proposed studies will clarify the behavioral conditions in which the basal forebrain cholinergic system is operative, and will test hypotheses concerning the ascending components of the model. These include an examination of the role of visceral afference in modulating behavioral and autonomic reactivity in anxiogenic contexts, by means of subdiaphragmatic vagotomy and other approaches. The proposed studies bear on the fundamental nature of anxiety and the underlying neural mechanisms that link behavioral processes and autonomic functions. These are important issues given the prevalence of anxiety disorders, and the fact that anxiolytic benzodiazepine receptor agonists are the most widely prescribed psychopharmacological agents worldwide. Because anxiety disorders are often associated with abnormal autonomic regulation, they represent a clear risk factor for cardiovascular disease and sudden cardiac death.