PSYCHOPHYSIOLOGY AND ANXIOGENESIS

拟议的研究将确定的心理生理组成部分， 行为和行为诱导的焦虑，并将测试 关于核心机制的具体假设 焦虑刺激对心血管的影响。苯二氮卓受体 (BZR)激动剂代表原型抗焦虑剂，而BZR逆转 已经提出激动剂具有致焦虑作用。我们的初步 研究揭示了增强的心血管反应的特定模式， 与致焦虑作用一致，在假条件反射动物中， 用BZR部分反向激动剂FG 7142处理的动物。这 过度的心血管反应似乎是由前脑介导的， 胆碱能机制，因为它可以被脑室内阻断 阿托品，并通过脑室内卡巴胆碱模拟。拟议 研究将证实这些初步发现，并进一步澄清 这种增强的心血管反应的性质和自主起源， 以及它发生的行为背景。其他研究 将检验这种心血管反应模式是 由中枢胆碱能机制介导。这将是完成 通过选择性损害基底前脑胆碱能系统， 胆碱能特异性神经毒素192 IgG-皂草素。基础的作用 前脑（胆碱能）终末野将进一步评价， 将胆碱能拮抗剂的中枢输注到脑的特定区域， 杏仁核、下丘脑后部和内侧前额叶皮质。结果 将增强我们对心理生理相关性的理解， 焦虑，以及行为和自主神经之间的潜在中心联系， 焦虑状态的表现。他们将进一步奠定重要的 研究自主成分的作用的基础 焦虑刺激的行为影响，以及对特定神经元的影响， 焦虑的潜在机制

The proposed research will identify psychophysiological components of pharmacologically and behaviorally-induced anxiogenesis, and will test specific hypotheses concerning the central mechanisms underlying the cardiovascular effects of anxiogenic stimuli. Benzodiazepine receptor (BZR) agonists represent prototypic antianxiety agents, while BZR inverse agonists have been suggested to have anxiogenic effects. Our preliminary studies reveal a specific pattern of potentiated cardiovascular response, consistent with an anxiogenic effect, in pseudoconditioned animals and animals treated with the BZR partial inverse agonist FG 7142. This exaggerated cardiovascular response appears to be mediated by a forebrain cholinergic mechanism, because it can be blocked by intraventricular atropine and is mimicked by intraventricular carbachol. The proposed studies will confirm these preliminary findings and further clarify the nature and autonomic origins of this potentiated cardiovascular response, as well as the behavioral contexts in which it occurs. Additional studies will test the hypothesis that this pattern of cardiovascular response is mediated by a central cholinergic mechanism. This will be accomplished by selective lesions of basal forebrain cholinergic systems with the cholinergic-specific neurotoxin 192 IgG-saporin. The role of basal forebrain (cholinergic) terminal fields will be further evaluated by central infusions of cholinergic antagonists into specific regions of the amygdala, posterior hypothalamus, and medial prefrontal cortex. Results will enhance our understanding of the psychophysiological correlates of anxiety, and the potential central links between behavioral and autonomic manifestations of anxiety states. They will further lay important groundwork for studies on the role of autonomic components in the behavioral effects of anxiogenic stimuli, and on the specific neural mechanisms underlying anxiety.