NITRIC OXIDE AND CHOLINERGIC ACTIVITY IN SCHIZOPHRENIA

描述（来自申请人摘要）： 在精神分裂症中，人们假设感觉门控 异常可能是个体潜在的遗传缺陷， 大脑改变其对重复刺激的敏感性，即，感官 门控精神分裂症患者通常是重度吸烟者， 目前认为，一个短暂的有益的治疗影响它， 通过吸烟对大脑感觉处理的影响来实现。虽然这 影响与尼古丁的尼古丁胆碱能作用有关， 发现尼古丁能发生快速脱敏， 受体表明，另一个更长寿的调节可能是 与尼古丁对这些患者的治疗效果有关。的 应用程序的目的将是调查的假设， 海马电路的烟碱能激活将导致 在感觉门控中， 一氧化氮的细胞外水平在离散的解剖区域 海马体 这些研究将使用最近开发的 微伏安传感器是非常有选择性和敏感的直接 空间和时间分辨的措施，NO的变化， 大脑的细胞外空间。这些研究将调查 胆碱能激动剂和NO释放拮抗剂在脑内的作用 大鼠海马脑片细胞外间隙，麻醉大鼠， 自由移动的动物此外，潜在的相互关系 将研究感觉门控和NO信号之间的关系， 进化的潜力和NO释放在同一动物。研究应 有助于更好地理解可能是 参与大鼠海马中NO信号传导，以及潜在的作用 精神分裂症中的NO

DESCRIPTION (from applicant's abstract): In schizophrenia, it has been hypothesized that sensory gating abnormalities may be an underlying inherited deficit in the individuals brain that alters its sensitivity to repeated stimuli, i.e., sensory gating. Patients with schizophrenia are often heavy smokers and it is currently believed that a short-lived beneficial therapeutic affect it achieved through smoking on brain sensory processing. Although this affect is involved with the nicotinic cholinergic effects of nicotine, the finding of rapid desensitization which occurs to nicotinergic receptors suggests that another more long-lived modulatory may be involved with the therapeutic effects of nicotine in these patients. The purpose of the application will be to investigate the hypotheses that nicotinergic activation of hippocampal circuitry will lead to changes in sensory gating that are mediated, in part, through increases in extracellular levels of nitric oxide in discrete anatomical regions of the hippocampus. These studies will be conducted using a recently developed microvoltammetric sensor that is very selective and sensitive for direct spatially and temporally resolved measures of NO changes in the extracellular space of the brain. These studies will investigate the effects of cholinergic agnonists and antagonists of NO release in the extracellular space of the rat hippocampus slices, anethesized rats and free-moving animals. In addition, the potential interrelationships between sensory gating and NO signaling will be investigated measuring evolved potentials and NO release in the same animal. The studies should contribute to a better understanding of AChergic mechanisms that may be involved in NO signaling in the rat hippocampus, and potential role(s) of NO in schizophrenia.