PSYCHOPHYSIOLOGY AND ANXIOGENESIS

拟议的研究将确定心理生理学成分 药物和行为诱导的焦虑症，并将测试 关于中枢机制的具体假设 焦虑性刺激的心血管效应。苯二氮卓类受体 (BZR)激动剂代表典型的抗焦虑药物，而BZR相反 激动剂被认为具有引发焦虑的作用。我们的预赛 研究揭示了一种增强心血管反应的特定模式， 与引起焦虑的效应一致，在假条件动物和 用BZR部分反向激动剂FG7142处理的动物。这 夸大的心血管反应似乎是由前脑调节的 胆碱能机制，因为它可以被脑室内阻断 阿托品，并被脑室内的卡巴胆碱模拟。建议数 研究将证实这些初步发现，并进一步澄清 这种增强心血管反应的自然和自主神经来源， 以及它发生的行为背景。其他研究 将检验这样一种假设，即这种心血管反应模式 由中枢胆碱能机制调节。这将会实现的 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-Saporin。基础设施的作用 前脑(胆碱能)终末区域将通过以下方式进一步评估 中枢注射胆碱能拮抗剂至大脑中隔核特定区域 杏仁核、下丘脑后部和内侧前额叶皮质。结果 将加强我们对心理生理学相关性的理解 焦虑，以及行为和自主神经之间潜在的中枢联系 焦虑状态的表现。他们将进一步发挥重要作用 自主神经成分在脑损伤中作用的研究基础 焦虑性刺激的行为效应，以及对特定神经的影响 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.