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: 6126204
• 负责人: Greg A. Gerhardt
• 金额: $ 16.35万
• 依托单位: UNIVERSITY OF KENTUCKY
• 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 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6126204
• 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（来自申请人的摘要）： 在精神分裂症中，已经假设感觉门控 异常可能是个人的潜在遗传赤字 改变其对重复刺激的敏感性的大脑，即感觉 门控。精神分裂症患者通常是吸烟者，这是 目前认为短暂的有益治疗会影响它 通过吸烟在大脑感觉处理上实现。虽然这个 情感与尼古丁的烟碱胆碱能作用有关， 烟碱能的快速脱敏的发现 受体表明，另一个更长寿的调节可能是 涉及尼古丁在这些患者中的治疗作用。这 申请的目的是调查 海马电路的烟碱能激活将导致变化 在感官门控在某种程度上通过增加而介导的 离散解剖区域中一氧化氮的细胞外水平 海马。 这些研究将使用最近开发的 微电算术传感器非常有选择性和敏感直接 在空间和时间上解决无变化的度量 大脑的细胞外空间。这些研究将研究 在 大鼠海马切片的细胞外空间，牙齿化大鼠和 自由移动的动物。此外，潜在的相互关系 在感官门控和未进行未信号的测量之间 进化的潜力，没有释放在同一动物中。研究应该 有助于更好地理解可能是Achergic机制 涉及大鼠海马中的无信号传导，并且潜在作用 精神分裂症中的NO。