Combined mGluR5 PET and fMRI imaging of Sex Differences during Cocaine Withdrawal

可卡因戒断期间性别差异的 mGluR5 PET 和 fMRI 联合成像

基本信息

  • 批准号:
    9331813
  • 负责人:
  • 金额:
    $ 72.02万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-06-01 至 2022-03-31
  • 项目状态:
    已结题

项目摘要

Project Summary There is compelling preclinical, epidemiological and clinical evidence of greater vulnerability in females for cocaine effects, including reward magnitude and positive subjective effects, rate of development of cocaine use disorder (CUD), and relapse risk following cocaine abstinence. Preclinical studies have demonstrated opposing effects of estradiol (activating) and progesterone (dampening) on behavioral and neurological responses to cocaine. The glutamate (Glu) system plays a central role in cocaine use, contributing to development and maintenance of regular use, withdrawal, and reinstatement following abstinence. Importantly, recent brain imaging studies have shown significant reductions in mGluR5 binding potential (BPND) during cocaine abstinence. To date, however, CUD human brain imaging studies have enrolled only male subjects or have included too few female subjects to permit analyses as a function of sex. The proposed research will examine sex differences in mGluR5 BPND during cocaine withdrawal as a function of gonadal hormones in women and men with cocaine use disorder and in a comparison group of healthy controls. In response to reviewer concerns, this revised application adds fMRI scans to broaden examination of sex differences in neurocircuitry that is activated in parallel with the targeted glutamate system during cocaine withdrawal. fMRI procedures will include both resting state functional connectivity scans (rsFC) as well as cocaine cue-induced event-related scans (CC) to occur within-subject during cocaine abstinence. We are specifically adding cueing procedures because it is known that women are more sensitive to craving and other associated effects of cocaine cues, during the follicular phase of menses. We will enroll 20 female and 20 male non-treatment seeking CUD participants. On day 1, CUD subjects undergo cocaine infusion, complete positron emission tomography (PET) imaging using [18F]FPEB to quantify mGluR5 BPND, followed by rsFC and CC fMRI. Women will be in the luteal phase of their menstrual cycle. During the 15-day CRU stay, bloods will be collected for measurement of hormones, and subjects will complete measures of withdrawal severity, craving and mood. On day 15, subjects will undergo a second set of [18F]FPEB PET and fMRI scans. This proposal will be the first to: characterize mGluR5 in women and men with CUD; examine the relationship of mGluR5 to resting state and cocaine cued brain function and to key behavioral measures of cocaine withdrawal and craving. Most importantly, the potential role of sex hormones in these effects will be studied. Despite over three decades of research, there are no efficacious pharmacotherapies approved for cocaine treatment. Thus, there is a pressing need to identify new neurotransmitter targets for medication development and to address gender- specific treatment needs. Findings may inform personalized, sex specific interventions for cocaine treatment.
项目总结

项目成果

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专利数量(0)

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MARY E MCCAUL其他文献

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{{ truncateString('MARY E MCCAUL', 18)}}的其他基金

Project 2-Optimization of Post-Transplant care via Biomarkers and Behavioral Interventions
项目 2 - 通过生物标志物和行为干预优化移植后护理
  • 批准号:
    10356014
  • 财政年份:
    2019
  • 资助金额:
    $ 72.02万
  • 项目类别:
Project 2-Optimization of Post-Transplant care via Biomarkers and Behavioral Interventions
项目 2 - 通过生物标志物和行为干预优化移植后护理
  • 批准号:
    10093987
  • 财政年份:
    2019
  • 资助金额:
    $ 72.02万
  • 项目类别:
Project 2-Optimization of Post-Transplant care via Biomarkers and Behavioral Interventions
项目 2 - 通过生物标志物和行为干预优化移植后护理
  • 批准号:
    10560559
  • 财政年份:
    2019
  • 资助金额:
    $ 72.02万
  • 项目类别:
Combined mGluR5 PET and fMRI imaging of Sex Differences during Cocaine Withdrawal
可卡因戒断期间性别差异的 mGluR5 PET 和 fMRI 联合成像
  • 批准号:
    9897512
  • 财政年份:
    2017
  • 资助金额:
    $ 72.02万
  • 项目类别:
Alcohol and Comorbid Tobacco Use Disorders: PET Imaging of Glutamate System Effects
酒精和烟草使用障碍:谷氨酸系统影响的 PET 成像
  • 批准号:
    9285689
  • 财政年份:
    2015
  • 资助金额:
    $ 72.02万
  • 项目类别:
HOMOCYSTEINE, A CANDIDATE PERIPHERAL BIOMARKER FOR CEREBRAL mGluR5 ACTIVITY IN COMORBID ALCOHOL- AND TOBACCO USE DISORDER
同型半胱氨酸,酒精和烟草使用障碍中大脑 mGluR5 活性的候选外周生物标志物
  • 批准号:
    9479534
  • 财政年份:
    2015
  • 资助金额:
    $ 72.02万
  • 项目类别:
Stress Effects on Alcohol Consumption: Age of onset and genes in heavy drinkers
压力对饮酒的影响:酗酒者的发病年龄和基因
  • 批准号:
    8606722
  • 财政年份:
    2012
  • 资助金额:
    $ 72.02万
  • 项目类别:
8/8: INIA Stress and Chronic Alcohol Interactions: Glucocorticoid antagonists in heavy drinkers:effects on fMRI connectivity, withdrawal and drinking
8/8:INIA 压力和慢性酒精相互作用:重度饮酒者中的糖皮质激素拮抗剂:对功能磁共振成像连接、戒断和饮酒的影响
  • 批准号:
    9242249
  • 财政年份:
    2012
  • 资助金额:
    $ 72.02万
  • 项目类别:
Stress Effects on Alcohol Consumption: Age of onset and genes in heavy drinkers
压力对饮酒的影响:酗酒者的发病年龄和基因
  • 批准号:
    8425097
  • 财政年份:
    2012
  • 资助金额:
    $ 72.02万
  • 项目类别:
Stress Effects on Alcohol Consumption: Age of onset and genes in heavy drinkers
压力对饮酒的影响:酗酒者的发病年龄和基因
  • 批准号:
    8230145
  • 财政年份:
    2012
  • 资助金额:
    $ 72.02万
  • 项目类别:

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