Amphetamine, cortical acetylcholine and cognition

安非他明、皮质乙酰胆碱和认知

• 批准号: 6822617
• 负责人: MARTIN F SARTER
• 金额: $ 20.83万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6822617
• 关键词: Amphetamine; cortical; acetylcholine; cognition

EXCEED THE SPACE PROVIDED. Cognitive variables are associated with the development of the positive symptoms of schizophrenia. Specifically, persistent impairments in the ability to filter irrelevant stimuli and associations, and in related executive functions such as set switching, planning, and dual-task performance, have been hypothesized to impede the patient's efficacy in using and updating past experiences to interpret and properly respond to current inputs. The proposed research will test the general hypothesis that increases in dopaminergic transmission in the nucleus accumbens (NAC), now widely accepted as a neuronal hallmark of schizophrenia, contribute trans-synaptically to the increases in (re)activity of cortical cholinergic inputs, and that the increased cortical cholinergic transmission mediates attentional impairments. Preliminary data demonstrate that the repeated administration of amphetamine (AMPH), a procedure that sensitizes the mesolimbic dopaminergic system, results in augmented increases in cortical acetylcholine (ACh) efflux in na'l've animals. Furthermore, repeated AMPH exposure results in attentional impairments in rats tested in a sustained attention task. Partial loss of cortical cholinergic inputs attenuated the attentional consequences of repeated AMPH administration. Additional preliminary data support the hypotheses that cortical ACh efflux is modulated by the NAC, presumably via projections to the basal forebrain, and that cortical ACh efflux and attentional performance are regulated by basal forebrain GABAergic and glutamatergic mechanisms. The proposed experiments will test hypotheses about the effects of repeated AMPH on attentional performance-associated cortical ACh efflux, the necessity of cortical cholinergic inputs in the manifestation of repeated AMPH-induced attentional impairments, and about basal forebrain afferent neuronal circuits that mediate the effects of repeated AMPH on attentional )erformance and performance-associated cortical ACh efflux. PERFORMANCE SITE ========================================Section End===========================================

超过提供的空间。认知变量与精神分裂症阳性症状的发展有关。具体而言，已经假设，持续过滤无关的刺激和关联的能力以及相关的执行功能（例如设置切换，计划和双重任务绩效）的损害已被假设，以妨碍患者在使用和更新过去的经验方面的功效，以解释和正确响应当前的投入。拟议的研究将检验一个总体假设，即振隔核（NAC）中多巴胺能传播的增加，现在被广泛接受为精神分裂症的神经元标志，在（重复）皮质胆碱能输入的（RE）活性增加的促进性促进性促进性疾病的传播症状上增加了皮质的传播，并提高了皮质胆汁芯粒细胞化的影响。初步数据表明，苯丙胺的重复给药（AMPH）是一种使中唇多巴巴胺能系统敏感的程序，导致Na'l've动物中皮质乙酰胆碱（ACH）外排的增长增加。此外，重复的AMPH暴露会导致在持续注意任务中测试的大鼠注意力障碍。皮质胆碱能输入的部分损失减弱了反复给药的注意力后果。额外的初步数据支持假设皮质ACH外排受到NAC的调节，大概是通过对基础前脑的投射来调节的，并且皮质ACH外排和注意力表现受到基础前脑GABAEGIC和谷氨酸能机制的调节。提出的实验将检验有关反复AMPH对注意力相关的皮质ACH外排的影响的假设，皮质胆碱能输入的必要性在反复的AMPH引起的注意力障碍的表现中以及基底脑前脑相关型神经元循环的反复效应和伴随效果的效果。表演站点=============================================================================================