Neuroactive Steroids,Dopamine and Cocaine Sensitization
神经活性类固醇、多巴胺和可卡因致敏
基本信息
- 批准号:6751694
- 负责人:
- 金额:$ 24.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-05-01 至 2006-04-30
- 项目状态:已结题
- 来源:
- 关键词:behavior testbehavioral /social science research tagbehavioral habituation /sensitizationchemical structure functioncocainecravingdopaminedrug addictiondrug administration rate /durationglutamate receptorlaboratory ratmicrodialysisneural information processingneural plasticityneural transmissionneurochemistryneuropharmacologyneuroregulationneurotransmitter antagonistnucleus accumbenspharmacokineticsrelapse /recurrenceself medicationstatistics /biometrysteroidssubstance abuse related behavior
项目摘要
DESCRIPTION (provided by applicant): The mesotelencephalic dopamine system is
implicated in the etiologies of schizophrenia and Parkinson's disease as well
as in the reinforcing properties of psychostimulants, including cocaine and
amphetamine. Recent evidence from our laboratory indicates that a number of
neuroactive steroids influence dopamine transmission in the striatum by
potentiating or inhibiting ionotropic glutamate receptor function. The major
objective of this project is to follow up on these findings by assessing the
activity of these neuroactive steroids in the nucleus accumbens, the limbic
portion of the striatal complex that is the locus for the reinforcing effects
of many drugs of abuse. To that end, we will assess the modulatory influence of
neuroactive steroids on the behavioral and neurochemical effects of ionotropic
glutamate receptor agonists in the core and shell of the nucleus accumbens.
Using microdialysis (coupled with HPLC-EC and HPLC-MS) and behavioral
techniques we will determine, i) the accumulation of systemically administered
neuroactive steroids in the brain, ii) the behavioral and neurochemical
consequences of neuroactive steroid modulation of ionotropic glutamate
receptors in the nucleus accumbens shell, iii) the influence of neuroactive
steroids on the initiation of behavioral sensitization to cocaine and iv) the
influence of neuroactive steroids on cocaine priming-induced reinstatement of
cocaine-seeking behavior. Collectively, these experiments will provide
information on the activity of neuroactive steroids in the CNS, which will be
invaluable for the development of steroids as potential pharmacological
treatments for disorders involving ionotropic glutamate receptors in general
and the craving associated with cocaine addiction in particular.
描述(由申请人提供):中脑多巴胺系统是
与精神分裂症和帕金森病的病因有关
如精神兴奋剂的增强特性,包括可卡因和
安非他明我们实验室的最新证据表明,
神经活性类固醇通过以下方式影响纹状体中的多巴胺传递:
增强或抑制离子型谷氨酸受体功能。主要
该项目的目标是通过评估
这些神经活性类固醇在丘脑核、边缘核、
纹状体复合体的一部分,是增强效应的场所
许多滥用药物。为此,我们将评估
神经活性类固醇对促离子化剂的行为和神经化学作用
谷氨酸受体激动剂的核心和壳的核。
使用微透析(结合HPLC-EC和HPLC-MS)和行为分析,
我们将确定的技术,i)全身给药的累积
大脑中的神经活性类固醇,ii)行为和神经化学
离子型谷氨酸的神经活性类固醇调节的结果
受体的影响,iii)神经活性的影响,
类固醇对可卡因行为敏化的起始作用,以及iv)
神经活性类固醇对可卡因诱发脑功能恢复影响
寻求可卡因的行为总的来说,这些实验将提供
关于CNS中神经活性类固醇活性的信息,
对于类固醇作为潜在药理学的发展是非常宝贵的
涉及离子型谷氨酸受体的疾病的一般治疗方法
尤其是与可卡因成瘾相关的渴望。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Inhibition of NMDA-induced striatal dopamine release and behavioral activation by the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate.
神经活性类固醇 3α-羟基-5β-孕-20-一半琥珀酸酯抑制 NMDA 诱导的纹状体多巴胺释放和行为激活。
- DOI:10.1046/j.1471-4159.2003.01814.x
- 发表时间:2003
- 期刊:
- 影响因子:4.7
- 作者:Sadri-Vakili,G;Johnson,DW;Janis,GC;Gibbs,TT;Pierce,RC;Farb,DH
- 通讯作者:Farb,DH
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David H Farb其他文献
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{{ truncateString('David H Farb', 18)}}的其他基金
Age-related Hypertension and Vascular Cognitive Impairment
年龄相关性高血压和血管性认知障碍
- 批准号:
10375761 - 财政年份:2022
- 资助金额:
$ 24.23万 - 项目类别:
Age-related Hypertension and Vascular Cognitive Impairment
年龄相关性高血压和血管性认知障碍
- 批准号:
10558579 - 财政年份:2022
- 资助金额:
$ 24.23万 - 项目类别:
Age-Related Changes in Neural Network Activity and Tau in a rat model of Alzheimer's Disease
阿尔茨海默病大鼠模型中神经网络活动和 Tau 蛋白与年龄相关的变化
- 批准号:
9530214 - 财政年份:2018
- 资助金额:
$ 24.23万 - 项目类别:
Neuroactive Steroids,Dopamine and Cocaine Sensitization
神经活性类固醇、多巴胺和可卡因致敏
- 批准号:
6624278 - 财政年份:2002
- 资助金额:
$ 24.23万 - 项目类别:
Neuroactive Steroids,Dopamine and Cocaine Sensitization
神经活性类固醇、多巴胺和可卡因致敏
- 批准号:
6473346 - 财政年份:2002
- 资助金额:
$ 24.23万 - 项目类别: