PRENATAL COCAINE AND DOPAMINE RECEPTOR SIGNALING
PRENATAL COCAINE AND DOPAMINE RECEPTOR SIGNALING
批准号:
6549360
负责人:
EITAN FRIEDMAN
金额:
$13.57万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-04-15 至 2003-03-31
关键词:
G protein cocaine developmental neurobiology dopamine receptor drug abuse embryo /fetus cell /tissue embryo /fetus drug adverse effect fatty acylation immunoprecipitation ion exchange chromatography laboratory rabbit neuropharmacology palmitates phosphatidylinositols placental transfer posttranslational modifications pregnancy receptor coupling receptor sensitivity
中文摘要
皮质醇穿过胎盘并诱发神经行为异常
在母亲怀孕期间摄入这种兴奋剂的后代中,
表明可卡因的目标是发育中的大脑。 可卡因
竞争性抑制突触多巴胺(DA)和其他
单胺,从而增加突触浓度
已知影响发育的神经递质,
CNS的成熟。 因此,有人假设,
中枢神经系统成熟过程中突触递质浓度的变化,
细胞和神经化学的适应性变化,
行为失常 在以前的调查中,我们
表明兔子出生前接触可卡因1)减少了
D1 DA受体与皮质和纹状体中的Galphas蛋白偶联,
2)减少皮层DA的诱发释放。
在出生后10至100天观察。 拟议将
观察到多巴胺能神经传递的持续功能变化
产前可卡因后是脱敏的后果,
D1 DA系统,这是由于可卡因诱导的损伤,
妊娠期间的神经递质系统。 拟议的研究旨在
明确了导致
D1 DA受体转导系统的解偶联和功能性
这种影响对DA神经传递的后果。具体地说,
实验的目的是:1)探索翻译后的作用
修饰的Galphas和D1受体在产生解偶联的
D1受体系统,2)确定D1在发育的早期
受体与Gs解偶联,3)测试D1受体是否也
与连接到磷脂酰肌醇的Galphaq解偶联
水解,4)测试D1受体-Gs解偶联是否导致
D1受体介导的功能脱敏,和5)测试
产前可卡因治疗在以下方面影响的特异性:
脑区、神经递质系统和受体亚型。
了解子宫内可卡因损害正常
神经发育并产生其长期的神经行为
异常最终将使我们能够设计特定的策略,
预防或对付可卡因滥用的后果,
怀孕
英文摘要
Cocaine crosses the placenta and induces neurobehavioral abnormalities
in offsprings of mothers ingesting this stimulant during pregnancy, thus
suggesting that cocaine targets the developing brain. Cocaine
competitively inhibits the removal of synaptic dopamine (DA) and other
monoamines and thus increases synaptic concentrations of
neurotransmitters which are known to influence the development and
maturation of the CNS. It was therefore hypothesized that the increase
in synaptic transmitter concentrations during CNS maturation results in
cellular and neurochemical adaptive changes which lead to long term
behavioral aberrations. In previously performed investigations, we
demonstrated that prenatal exposure of rabbits to cocaine 1) reduced
coupline of D1 DA receptors to Galphas protein in cortex and striatum,
and 2) diminished evoked release of cortical DA. These effects were
observed on postnatal days 10 to 100. It is proposed that the
persistent functional changes in dopaminergic neurotransmission observed
after prenatal cocaine are the consequences of desensitization of the
D1 DA system that results from cocaine-induced insult to this
neurotransmitter system during gestation. The proposed studies aim at
defining the molecular mechanisms responsible for the apparent
uncoupling of the D1 DA receptor transduction system and the functional
consequences of this effect on DA neurotransmission. Specifically,
experiments are designed to 1) explore the role of posttranslational
modifications of Galphas and of D1 receptors in producing uncoupling of
the D1 receptor system, 2) establish how early in development D1
receptors uncouple from Gs, 3) test whether the D1 receptor also
uncouples from Galphaq which is linked to phosphatidylinositol
hydrolysis, 4) test whether D1 receptor-Gs uncoupling results in
desensitization of D1 receptor-mediated functions, and 5) test the
specificity of the effects of prenatal cocaine treatment in terms of
brain region, neurotransmitter system, and receptor subtype.
Understanding the mechanism by which in utero cocaine impairs normal
neurodevelopment and produces its long-term neurobehavioral
abnormalities will ultimately enable us to design specific strategies
to prevent or counter the consequences of cocaine abuse during
pregnancy.
期刊论文(6)
专著(0)
科研奖励(0)
会议论文
Prenatal exposure to cocaine disrupts D1A dopamine receptor function via selective inhibition of protein phosphatase 1 pathway in rabbit frontal cortex.
产前接触可卡因会通过选择性抑制兔额叶皮质中的蛋白磷酸酶 1 通路来破坏 D1A 多巴胺受体功能。
DOI:
10.1523/jneurosci.21-23-09160.2001
发表时间:
2001
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
作者:
[Zhen,X, Torres,C, Wang,HY, Friedman,E]
通讯作者:
Friedman,E
Attenuation of cocaine-induced genomic and functional responses in prenatal cocaine-exposed rabbits.
产前接触可卡因的兔子中可卡因诱导的基因组和功能反应减弱。
DOI:
10.1016/s0091-3057(01)00534-2
发表时间:
2001
期刊:
Pharmacology, biochemistry, and behavior
影响因子:
--
作者:
[Tilakaratne,N, Cai,G, Friedman,E]
通讯作者:
Friedman,E
MIDARP at CCNY
-
批准号:6863611
-
项目类别:
-
资助金额:$43.89万
-
财政年份:2005
-
负责人:EITAN FRIEDMAN
-
依托单位:
MIDARP at CCNY
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批准号:7234457
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项目类别:
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资助金额:$42.39万
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财政年份:2005
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负责人:EITAN FRIEDMAN
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依托单位:
MIDARP at CCNY
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批准号:7753147
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项目类别:
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资助金额:$42.99万
-
财政年份:2005
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负责人:EITAN FRIEDMAN
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依托单位:
MIDARP at CCNY
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批准号:7066112
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项目类别:
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资助金额:$44.52万
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财政年份:2005
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负责人:EITAN FRIEDMAN
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依托单位:
SIGNAL TRANSDUCTION IN BIPOLAR ILLNESS
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批准号:6542327
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项目类别:
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资助金额:$19.05万
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财政年份:1999
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负责人:EITAN FRIEDMAN
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依托单位:
SIGNAL TRANSDUCTION IN BIPOLAR ILLNESS
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批准号:6187078
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项目类别:
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资助金额:$25.54万
-
财政年份:1999
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负责人:EITAN FRIEDMAN
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依托单位:
SIGNAL TRANSDUCTION IN BIPOLAR ILLNESS
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批准号:6042274
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项目类别:
-
资助金额:$24.8万
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财政年份:1999
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负责人:EITAN FRIEDMAN
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依托单位:
SIGNAL TRANSDUCTION IN BIPOLAR ILLNESS
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批准号:6392713
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项目类别:
-
资助金额:$7.26万
-
财政年份:1999
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负责人:EITAN FRIEDMAN
-
依托单位:
DOPAMINE-LINKED PHOSPHOINOSITIDE METABOLISM IN BRAIN
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批准号:2839337
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项目类别:
-
资助金额:$19.65万
-
财政年份:1998
-
负责人:EITAN FRIEDMAN
-
依托单位:
PRENATAL COCAINE AND DOPAMINE RECEPTOR SIGNALING
-
批准号:6175490
-
项目类别:
-
资助金额:$23.57万
-
财政年份:1998
-
负责人:EITAN FRIEDMAN
-
依托单位:
PRENATAL COCAINE AND DOPAMINE RECEPTOR SIGNALING
-
批准号:6032281
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项目类别:
-
资助金额:$10.1万
-
财政年份:1998
-
负责人:EITAN FRIEDMAN
-
依托单位:
DOPAMINE-LINKED PHOSPHOINOSITIDE METABOLISM IN BRAIN
-
批准号:6038324
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1998
-
负责人:EITAN FRIEDMAN
-
依托单位:
DOPAMINE-LINKED PHOSPHOINOSITIDE METABOLISM IN BRAIN
-
批准号:6126233
-
项目类别:
-
资助金额:$20.24万
-
财政年份:1998
-
负责人:EITAN FRIEDMAN
-
依托单位:
PRENATAL COCAINE AND DOPAMINE RECEPTOR SIGNALING
-
批准号:6378678
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项目类别:
-
资助金额:$10.82万
-
财政年份:1998
-
负责人:EITAN FRIEDMAN
-
依托单位:
PRENATAL COCAINE AND DOPAMINE RECEPTOR SIGNALING
-
批准号:2619956
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项目类别:
-
资助金额:$12.12万
-
财政年份:1998
-
负责人:EITAN FRIEDMAN
-
依托单位:
PRENATAL COCAINE AND DOPAMINE RECEPTOR SIGNALING
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批准号:2898134
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项目类别:
-
资助金额:$22.88万
-
财政年份:1998
-
负责人:EITAN FRIEDMAN
-
依托单位:
DOPAMINE-LINKED PHOSPHOINOSITIDE METABOLISM IN BRAIN
-
批准号:2609629
-
项目类别:
-
资助金额:$19.08万
-
财政年份:1991
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负责人:EITAN FRIEDMAN
-
依托单位:
DOPAMINE-LINKED PHOSPHOINOSITIDE METABOLISM IN BRAIN
-
批准号:3416360
-
项目类别:
-
资助金额:$15.21万
-
财政年份:1991
-
负责人:EITAN FRIEDMAN
-
依托单位:
DOPAMINE-LINKED PHOSPHOINOSITIDE METABOLISM IN BRAIN
-
批准号:3416359
-
项目类别:
-
资助金额:$14.62万
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财政年份:1991
-
负责人:EITAN FRIEDMAN
-
依托单位:
DOPAMINE-LINKED PHOSPHOINOSITIDE METABOLISM IN BRAIN
-
批准号:2037438
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项目类别:
-
资助金额:$19.3万
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财政年份:1991
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负责人:EITAN FRIEDMAN
-
依托单位:
国内基金
海外基金
抗可卡因(Cocaine)抗体酶的研制及实验研究
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批准号:39570633
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项目类别:面上项目
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资助金额:8.5万元
-
批准年份:1995
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负责人:段燕文
-
依托单位: