PSYCHOPHYSIOLOGY AND ANXIOGENESIS

拟议的研究将确定的心理生理成分

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.