PSYCHOPHYSIOLOGY AND ANXIOGENESIS

描述(申请人摘要)：在这项竞争中提出的研究 更新应用程序将检查基底前脑皮质的作用 胆碱能系统在恐惧和心血管病患者的行为和心血管特征中的作用 焦虑。这项研究是由两个假设指导的：a)嘴 恐惧和焦虑的神经行为机制可以调节自主神经 控制，以及b)自主介导的内脏反应可以调节 中枢上升通路对焦虑相关环境的皮层处理。 后者包括基底前脑皮质胆碱能投射，它 与恐惧和心血管反应有关 焦虑。拟议的工作将进一步开发和测试一种神经生物学 恐惧和焦虑背后的中枢系统的模型。特别强调的是 基底前脑胆碱能系统及其在整合行为中的作用 和心血管反应。工作将确定相关的目标地点 中枢性脑内注射A_1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(192Ig G-Saporin)，以及胆碱能和 肾上腺素能药物和苯二氮卓类受体激动剂、拮抗剂和逆转剂 激动剂。其他拟议的研究将阐明 基底前脑胆碱能系统正在运作，并将进行测试 关于模型上升部分的假设。其中包括一个 内脏传入在调节行为和行为中的作用 在焦虑性环境中通过隔膜下的自主神经反应性 迷走神经切断术和其他入路。拟议的研究涉及以下基本问题 焦虑的本质和连接行为的潜在神经机制 过程和自主功能。这些是重要的问题，因为 焦虑症的流行，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。 全世界。因为焦虑症经常与异常联系在一起 自主调节，它们是心血管疾病的明显危险因素 疾病和心源性猝死。

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.