CCK AND MIDBRAIN DA SYSTEMS: SPECIFICITY OF ACTIONS
CCK AND MIDBRAIN DA SYSTEMS: SPECIFICITY OF ACTIONS
批准号:
3381211
负责人:
ARTHUR S FREEMAN
金额:
$6.09万
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-09-01 至 1991-08-31
关键词:
afferent nerve albino rat apomorphine brain cell brain electrical activity brain mapping caudate nucleus cell population study cholecystokinin computer data analysis dopamine dopamine receptor drug administration routes drug interactions electrophysiology electrostimulus hormone receptor injection /infusion mesencephalon neural transmission neurotransmitters nontherapeutic iontophoresis receptor sensitivity substantia nigra
中文摘要
多巴胺(DA)神经元的亚群,
中脑的A9和A10区域含有肽
胆囊收缩素(CCK)。 脑内和微离子导入
施用CCK有效地激发DA细胞亚群
其可以对应于也含有CCK的那些细胞。 在
除了这种短暂的兴奋,CCK发挥更持久的
对DA神经元敏感性的调节作用
静脉注射阿扑吗啡的抑制作用,
微离子电渗DA。初步研究表明,
CCK的兴奋和调节作用也可以发生
独立和不同的DA途径起源于
中脑似乎受到静脉内CCK的不同影响。
鉴于中脑DA系统与我们目前的
关于几种神经系统的神经生物学假设,
精神疾病,一系列的研究建议开始,
更详细地探索CCK与已鉴定DA的相互作用
神经元亚群 总的来说,
CCK研究一直受到缺乏具体和
强大的对手。 几种新的高活性CCK拮抗剂
对中枢和/或外周CCK受体的亲和力已经被
开发 在本发明的建议中,这些化合物将是
用于研究受体特异性的
CCK对已鉴定亚群的电生理效应
DA神经元 此外,直接和调节
CCK对纹状体神经元的电生理作用将是
表征并与刺激的效果进行比较,
纹状体CCK传入。 希望所获得的信息
这些研究将有助于更好地了解
不同的中脑DA神经元通路的生理学。 这
知识,结合解剖学和
生物化学技术,可能有助于制定可测试的
与中枢神经系统相关的疾病病因学假说
DA神经元功能障碍。
英文摘要
Subpopulations of dopamine (DA)-containing neurons within the
A9 and A10 regions of the midbrain contain the peptide
cholecysto-kinin (CCK). Intravenously and microiontophoretically
administered CCK potently excites a subpopulation of DA cells
that may correspond to those cells which also contain CCK. In
addition to this transient excitation, CCK exerts a more enduring
modulatory effect on DA neurons with regard to their sensitivity
to the inhibitory effects of intravenous apomorphine and
microiontophoretic DA. Preliminary studies have shown that the
excitatory and modulatory effects of CCK can also occur
independently and that distinct DA pathways originating in the
midbrain appear to be differentially affected by intravenous CCK.
Given the relevance of midbrain DA systems to our current
hypotheses regarding the neurobiology of several neurological and
psychiatric disorders, a series of studies are proposed to begin to
explore in more detail the interactions of CCK with identified DA
neuronal subpopulations. In general, advancements in the field of
CCK research have been hindered by the lack of specific and
potent antagonists. Several new CCK antagonists with high
affinity for central and/or peripheral CCK receptors have been
developed. In the present proposal, these compounds will be
employed to investigate the receptor specificity of the
electrophysiological effects of CCK on identified subpopulations
of DA neurons. In addition, the direct and modulatory
electrophysiological effects of CCK on striatal neurons will be
characterized and compared to the effects of stimulation of
striatal CCK afferents. It is hoped that the information obtained
from these studies will lead to a better understanding of the
physiology of distinct midbrain DA neuronal pathways. This
knowledge, combined with that obtained with anatomical and
biochemical techniques, may aid in the formulation of testable
hypotheses concerning the etiology of disorders linked to central
DA neuronal dysfunction.
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会议论文
EVALUATION OF PCP AND SIGMA EFFECTS ON DA PHYSIOLOGY
-
批准号:3214442
-
项目类别:
-
资助金额:$10.98万
-
财政年份:1991
-
负责人:ARTHUR S FREEMAN
-
依托单位:
EVALUATION OF PCP AND SIGMA EFFECTS ON DA PHYSIOLOGY
-
批准号:3214445
-
项目类别:
-
资助金额:$11.42万
-
财政年份:1991
-
负责人:ARTHUR S FREEMAN
-
依托单位:
CCK AND MIDBRAIN DA SYSTEMS--SPECIFICITY OF ACTIORS
-
批准号:2245365
-
项目类别:
-
资助金额:$9.88万
-
财政年份:1988
-
负责人:ARTHUR S FREEMAN
-
依托单位:
CCK AND MIDBRAIN DA SYSTEMS--SPECIFICITY OF ACTIONS
-
批准号:3381213
-
项目类别:
-
资助金额:$2.06万
-
财政年份:1988
-
负责人:ARTHUR S FREEMAN
-
依托单位:
CCK AND MIDBRAIN DA SYSTEMS: SPECIFICITY OF ACTIONS
-
批准号:3381207
-
项目类别:
-
资助金额:$6.68万
-
财政年份:1988
-
负责人:ARTHUR S FREEMAN
-
依托单位:
CCK AND MIDBRAIN DA SYSTEMS--SPECIFICITY OF ACTIONS
-
批准号:3381209
-
项目类别:
-
资助金额:$9.58万
-
财政年份:1988
-
负责人:ARTHUR S FREEMAN
-
依托单位:
CCK & MID-BRAIN DA SYSTEMS: SPECIFICITY OF ACTIORS
-
批准号:2245364
-
项目类别:
-
资助金额:$7.39万
-
财政年份:1988
-
负责人:ARTHUR S FREEMAN
-
依托单位:
CCK AND MIDBRAIN DA SYSTEMS: SPECIFICITY OF ACTIONS
-
批准号:3381212
-
项目类别:
-
资助金额:$6.27万
-
财政年份:1988
-
负责人:ARTHUR S FREEMAN
-
依托单位:
AGING AND MIDBRAIN DA ELECTROPHYSIOLOGY
-
批准号:3428667
-
项目类别:
-
资助金额:$3.88万
-
财政年份:1987
-
负责人:ARTHUR S FREEMAN
-
依托单位:
STUDIES OF A PUTATIVE SELECTIVE DA AUTORECEPTOR
-
批准号:3052434
-
项目类别:
-
资助金额:$0.65万
-
财政年份:1984
-
负责人:ARTHUR S FREEMAN
-
依托单位:
海外基金