PREFRONTAL CORTICAL REGULATION OF NUCLEUS ACCUMBENS

伏核的前额皮质调节

• 批准号: 6243072
• 负责人: EDWARD M STRICKER
• 金额: $ 23.34万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243072
• 关键词: amphetamines; aspartate; calcium flux; chordate locomotion; corticofugal system; developmental neurobiology; dopamine; dopamine receptor; electrophysiology; frontal lobe /cortex; gamma aminobutyrate; glutamates; hippocampus; laboratory rat; neuroanatomy; neurochemistry; neurons; neurotransmitters; nucleus accumbens; pathologic process; phencyclidine; psychological stressor; schizophrenia; temporal lobe /cortex disorder

This project explores the proposal that abnormalities in prefrontal cortex (PFC) are central to the etiology of schizophrenia; that they lead to dysregulation of mesolimbic dopamine (DA), particularly during stress; and that defects in the temporal lobe and PFC that arise early in development may result in the emergence of schizophrenic symptoms as the CNS matures. The project may be divided into three components: First, we will further define the alterations produced by PFC lesions on DA activity in accumbens. We will examine the impact of lesions of either DA afferents to PFC or excitatory efferents from PFC on extracellular DA levels in accumbens in the basal state and during acute and chronic stress. The impact of lesions of PFC on amphetamine- and phencyclidine (PCP)-induced changes in extracellular DA in accumbens and locomotor activity will also be studied. Second, we will examine the basic mechanisms that may underlie the modulation of subcortical DA systems by glutamatergic corticofugal projections from PFC. This will involve the monitoring of extracellular glutamate, aspartate, and GABA in accumbens of intact and PFC-lesioned animals, using dialysates previously analyzed for DA. If lesion-induced changes in excitatory amino acid availability are observed, we will determine the mechanisms by which such changes might influence accumbens DA by exploring interactions among the area's principal transmitters, as well as measuring the effects of PFC lesions on the electrophysiological activity of mesoaccumbens DA neurons and the impact of PFC lesions and of stress on the depolarization block produced by DA receptor antagonists. Finally, we will examine the functional impact of changes in DA receptor stimulation on the physiology of dopaminoceptive cells in accumbens, and how it is affected by manipulation of PFC corticofugal projections. The project involves a combination of in vivo and in vitro approaches, and utilizes neurochemical, anatomical, and electrophysiological techniques.

这个项目探讨的建议，异常的前额叶 皮质（PFC）是精神分裂症病因的核心;它们导致 中脑边缘多巴胺（DA）的失调，特别是在应激期间; 而颞叶和前额叶皮层的缺陷， 发展可能导致精神分裂症症状的出现， 中枢神经系统成熟。 该项目可分为三个部分：第一， 我们将进一步确定PFC病变对DA的影响， 活动中， 我们将研究病变的影响， DA传入PFC或PFC兴奋性传出细胞外DA 基础状态以及急性和慢性 应力 PFC损伤对苯丙胺和苯环己哌啶的影响 （PCP）诱导的多巴胺（DA）在运动神经元和运动神经元中的变化 活动也将进行研究。 第二，我们将研究基本的 可能是皮层下DA系统调制的基础机制， PFC的神经元能离皮质投射。这将涉及 监测细胞外谷氨酸，天冬氨酸，和GABA在Escherichia coli 完整和PFC损伤动物，使用先前分析的透析液 如果损伤引起兴奋性氨基酸可用性的变化， 我们将确定这种变化的机制， 通过探索该地区的 主要递质，以及测量PFC病变的影响 对中脑DA能神经元电生理活动的影响， PFC损伤和应力对产生的去极化阻滞的影响 DA受体拮抗剂。 最后，我们将检查函数 DA受体刺激的变化对神经元生理学的影响 多巴胺感受细胞的神经，以及它是如何受到影响， 操纵PFC离皮质投射。 该项目涉及一个 体内和体外方法的组合，并利用 神经化学、解剖学和电生理学技术。