Glutamate-Glutamine Cycling (Vcyc) in Cocaine Abstinence using 13C-MRS

使用 13C-MRS 进行可卡因戒断中的谷氨酸-谷氨酰胺循环 (Vcyc)

基本信息

  • 批准号:
    8861373
  • 负责人:
  • 金额:
    $ 45.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-05-15 至 2017-04-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Relapse remains a critical unmet challenge in the treatment of cocaine addiction. While many will succeed in initiating abstinence, the vast majority of cocaine abusers will experience multiple relapses over the course of their illness, and many will fail to achieve an enduring drug-free existence. Thus, the current lack of medications for reducing relapse risk remains a major gap in the clinical management of cocaine dependence. Two decades ago, seminal studies in chronic cocaine abusers (Volkow 1992, 1993) identified resting- state reductions in prefrontal cortical (PFC) glucose metabolism (as measured by [18F]-FDG PET) during states of sustained drug abstinence (> 1 week and up to 3 months). These deficits in neuroenergetics are believed to account for the neurocognitive impairments that underlie the impulsive actions, compulsive behaviors, and risky decisions that lead to relapse in cocaine addicts. Despite their clinical importance, the molecular basis of these deficits is still unknown today. The current exploratory-developmental R01 seeks to directly test whether deficits in PFC glucose metabolism are reflective of abnormal glutamate neurotransmission in light of: 1) data demonstrating the direct neurometabolic coupling of cortical glucose metabolism and glutamatergic neurotransmission (Belanger 2011); 2) the unique ability of isotopic ([13C]-glucose) magnetic resonance spectroscopy (13C- MRS) to simultaneously and noninvasively assess neuroenergetics (mitochondrial glucose oxidation or VTCA) and glutamatergic neurotransmission (glutamate-glutamine cycling or VCYC) in humans (Rothman 2011), and 3) preclinical evidence demonstrating the importance of dysregulated glutamate homeostasis in cocaine- and cue-induced reinstatement of drug-seeking (Kalivas 2009). If confirmed, the current study would set the stage for future prospective, controlled, biomarker-guided (VCYC) evaluations of candidate pharmacotherapies (e.g., N-acetylcysteine, ceftriaxone, riluzole and/or pentoxifylline) targeted at restoring glutamate homeostasis (i.e., based on up-regulation of glial proteins, such as GLT-1, that mediate glutamate cycling / neurometabolic coupling).


项目成果

期刊论文数量(0)
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ROBERT T MALISON其他文献

ROBERT T MALISON的其他文献

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{{ truncateString('ROBERT T MALISON', 18)}}的其他基金

Assessing Glutamate Homeostasis in Cocaine Addiction Using 7T 1H-MRS
使用 7T 1H-MRS 评估可卡因成瘾中的谷氨酸稳态
  • 批准号:
    9226608
  • 财政年份:
    2017
  • 资助金额:
    $ 45.92万
  • 项目类别:
Imaging Synaptic Density in the Cocaine-Addicted Brain In Vivo using 11C UCB J PET
使用 11C UCB J PET 对可卡因成瘾大脑中的突触密度进行体内成像
  • 批准号:
    9335542
  • 财政年份:
    2017
  • 资助金额:
    $ 45.92万
  • 项目类别:
Clinical and Educational Core
临床和教育核心
  • 批准号:
    7797222
  • 财政年份:
    2010
  • 资助金额:
    $ 45.92万
  • 项目类别:
A PET study of 5-HT1B receptor binding as a novel biomarker for cocaine dependenc
5-HT1B 受体结合作为可卡因依赖的新型生物标志物的 PET 研究
  • 批准号:
    7660275
  • 财政年份:
    2009
  • 资助金额:
    $ 45.92万
  • 项目类别:
DBH, D2High and Cocaine Paranoia/Aversion: A [11C]PHNO PET Study
DBH、D2High 和可卡因偏执/厌恶:[11C]PHNO PET 研究
  • 批准号:
    7924140
  • 财政年份:
    2009
  • 资助金额:
    $ 45.92万
  • 项目类别:
DBH, D2High and Cocaine Paranoia/Aversion: A [11C]PHNO PET Study
DBH、D2High 和可卡因偏执/厌恶:[11C]PHNO PET 研究
  • 批准号:
    7762102
  • 财政年份:
    2009
  • 资助金额:
    $ 45.92万
  • 项目类别:
Patient-Oriented Research and Mentoring in the Translational Neurobiology/Genetic
转化神经生物学/遗传学中以患者为导向的研究和指导
  • 批准号:
    7322945
  • 财政年份:
    2007
  • 资助金额:
    $ 45.92万
  • 项目类别:
Patient-Oriented Research and Mentoring in the Translational Neurobiology/Genetic
转化神经生物学/遗传学中以患者为导向的研究和指导
  • 批准号:
    7477867
  • 财政年份:
    2007
  • 资助金额:
    $ 45.92万
  • 项目类别:
Patient-Oriented Research and Mentoring in the Translational Neurobiology/Genetic
转化神经生物学/遗传学中以患者为导向的研究和指导
  • 批准号:
    8033210
  • 财政年份:
    2007
  • 资助金额:
    $ 45.92万
  • 项目类别:
Patient-Oriented Research and Mentoring in the Translational Neurobiology/Genetic
转化神经生物学/遗传学中以患者为导向的研究和指导
  • 批准号:
    8233537
  • 财政年份:
    2007
  • 资助金额:
    $ 45.92万
  • 项目类别:

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