fMRI Characterization of Acute Tolerance to Cocaine

可卡因急性耐受性的功能磁共振成像表征

基本信息

  • 批准号:
    6799747
  • 负责人:
  • 金额:
    $ 17.75万
  • 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:
    2002-08-25 至 2006-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: (provided by the applicant) The action of cocaine on the central nervous system is complex. Development of acute tolerance to cocaine has been investigated extensively and has been described in both human and animal studies. Acute tolerance is characterized by rapid and sometimes complete loss of behavioral and cardiovascular efficacy of cocaine after prolonged or repeated acute exposure despite a stable, elevated plasma concentration. As indicated by both our preliminary data collected in rats using fMRI to elucidate regions of local neural stimulation and supported by behavioral data in humans, while bolus administration of cocaine stimulates neuronal activity in multiple brain structures, a prolonged infusion results in a progressive reversal of this stimulation process. Therefore, the central hypothesis to be tested by this application is that cocaine acts not only to stimulate neural activity in brain but also to terminate and/or reverse activation in stimulated structures and that this process of acute inactivation is suppressed in the chronically cocaine-exposed state. The purpose of these experiments are three fold. Firstly, they are designed to establish that the reversal of fMRI signal observed during a prolonged, constant infusion of cocaine reflects a cocaine-dependent process exerted upon structures activated by cocaine. Furthermore, we will demonstrate that rapid repeated administration of cocaine produces acute tolerance to the stimulating effects. Secondly, we will demonstrate that the reversal of fMRI activation signal accurately reflects a decrease in neuronal activity in cocaine activated brain structures. Because of the importance of dopamine and the D1 receptor both in brain reward circuitry and the mechanism of central stimulation induced by cocaine, we will investigate the relationship between dopamine release and cocaine-mediated reversal of cocaine induced brain activation. Specifically, we will correlate changes in synaptic dopamine with generation and termination of activation signal. Thirdly, using a rat model of chronic exposure to cocaine in which rats are trained to self-administer drug, we will demonstrate that mesolimbic structures are sensitive to repeated prior exposure to cocaine which results to a shift in the balance between activation and acute inactivation within these regions.
描述:(由申请人提供)

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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JOHN J. A. MAROTA其他文献

JOHN J. A. MAROTA的其他文献

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{{ truncateString('JOHN J. A. MAROTA', 18)}}的其他基金

Predicting Brain Recovery after Acute Hemorrhage and Resuscitation
预测急性出血和复苏后的大脑恢复
  • 批准号:
    7894723
  • 财政年份:
    2009
  • 资助金额:
    $ 17.75万
  • 项目类别:
Predicting Brain Recovery after Acute Hemorrhage and Resuscitation
预测急性出血和复苏后的大脑恢复
  • 批准号:
    7472192
  • 财政年份:
    2009
  • 资助金额:
    $ 17.75万
  • 项目类别:
Functional Impact of Pain and Opioid Addiction on the Mesolimbic Dopaminergic Sys
疼痛和阿片类药物成瘾对中脑边缘多巴胺能系统的功能影响
  • 批准号:
    7608893
  • 财政年份:
    2008
  • 资助金额:
    $ 17.75万
  • 项目类别:
Effects of Cocaine Self-administration: fMRI of Awake Non-human Primates
可卡因自我给药的影响:清醒非人类灵长类动物的功能磁共振成像
  • 批准号:
    7134143
  • 财政年份:
    2006
  • 资助金额:
    $ 17.75万
  • 项目类别:
Effects of Cocaine Self-administration: fMRI of Awake Non-human Primates
可卡因自我给药的影响:清醒非人类灵长类动物的功能磁共振成像
  • 批准号:
    7296158
  • 财政年份:
    2006
  • 资助金额:
    $ 17.75万
  • 项目类别:
fMRI Characterization of Acute Tolerance to Cocaine
可卡因急性耐受性的功能磁共振成像表征
  • 批准号:
    6931471
  • 财政年份:
    2002
  • 资助金额:
    $ 17.75万
  • 项目类别:
fMRI Characterization of Acute Tolerance to Cocaine
可卡因急性耐受性的功能磁共振成像表征
  • 批准号:
    6649285
  • 财政年份:
    2002
  • 资助金额:
    $ 17.75万
  • 项目类别:
fMRI Characterization of Acute Tolerance to Cocaine
可卡因急性耐受性的功能磁共振成像表征
  • 批准号:
    6430177
  • 财政年份:
    2002
  • 资助金额:
    $ 17.75万
  • 项目类别:
Functional Impact of Pain and Opioid Addiction on the Mesolimbic Dopaminergic Sys
疼痛和阿片类药物成瘾对中脑边缘多巴胺能系统的功能影响
  • 批准号:
    7874690
  • 财政年份:
  • 资助金额:
    $ 17.75万
  • 项目类别:
Functional Impact of Pain and Opioid Addiction on the Mesolimbic Dopaminergic Sys
疼痛和阿片类药物成瘾对中脑边缘多巴胺能系统的功能影响
  • 批准号:
    8291425
  • 财政年份:
  • 资助金额:
    $ 17.75万
  • 项目类别:

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