NITRIC OXIDE AND CHOLINERGIC ACTIVITY IN SCHIZOPHRENIA

精神分裂症中的一氧化氮和胆碱能活性

• 批准号: 2763652
• 负责人: Greg A. Gerhardt
• 金额: $ 2.27万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-15 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2763652
• 关键词: brain metabolism; dentate gyrus; electrical measurement; electrodes; evoked potentials; experimental brain lesion; hippocampus; histology; laboratory rat; monitoring device; neural conduction; neuropharmacology; nicotine; nicotinic receptors; nitric oxide; receptor expression; schizophrenia; sensory feedback

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.

描述(摘自申请人的摘要)： 在精神分裂症患者中，人们假设感觉门控 异常可能是个体潜在的遗传缺陷。 对重复刺激，即感觉，改变其敏感性的大脑 门控。精神分裂症患者通常是烟瘾很大的人，事实也是如此 目前认为，一种短暂的有益的治疗作用吧 这是通过吸烟对大脑的感觉处理来实现的。虽然这件事 情感与尼古丁的尼古丁胆碱能效应有关， 烟碱能快速脱敏的发现 受体提示，另一种更长寿的调节机制可能是 参与了尼古丁对这些患者的治疗效果。这个 申请的目的将是调查以下假设 烟碱能激活海马区回路将导致改变 在感觉门控中，部分是通过增加 三叉神经节不同解剖区域细胞外一氧化氮水平 海马体。 这些研究将使用最近开发的一种 微伏安型传感器，对直接电流有很高的选择性和灵敏度 空间和时间分辨率不变的量度 大脑的细胞外空间。这些研究将调查 胆碱能激动剂和NO释放拮抗剂对大鼠脑内NO释放的影响 大鼠海马片、去势大鼠和大鼠海马片细胞外间隙 自由活动的动物。此外，潜在的相互关系 感官门控和NO信号之间的关系将通过测量 在同一动物体内进化的潜力和NO的释放。这些研究应该 有助于更好地理解可能存在的 参与大鼠海马区NO信号传递及其潜在作用(S) 精神分裂症患者中的NO。