Influence of 5-HT1b Activation on the Abuse Related Effects of Cocaine

5-HT1b 激活对可卡因滥用相关影响的影响

基本信息

  • 批准号:
    10457811
  • 负责人:
  • 金额:
    $ 66.01万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-01 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Cocaine use disorder continues to be a significant public health concern. Despite strides in our understanding of the neurobiological underpinnings of cocaine addiction in preclinical models, a limited amount of research has translated those findings into clinical populations. Such translation is crucial to identify neurobiological circuits that contribute to the problems posed by cocaine use disorder and to guide treatment based on those clinical neuroscience findings. Cocaine potently inhibits the reuptake of serotonin (5-HT). Increased synaptic 5- HT resulting from this reuptake inhibition activates multiple 5-HT receptor subtypes. Some of these receptor subtypes have been implicated in the abuse-related effects of cocaine, including its primary reinforcing effects (i.e., cocaine taking behavior). 5-HT1b receptors play a particularly important role in cocaine effects, likely because they are highly expressed in the mesocorticolimbic system. Preclinical data show that zolmitriptan, a commercially available selective 5-HT1b agonist migraine medication approved for human use, selectively attenuates the reinforcing and other abuse-related effects of cocaine. The overarching goal of this project is to advance these promising preclinical findings into clinical populations, thereby demonstrating that the 5-HT1b system plays a key role in the effects of cocaine in humans. To this end, 20 non-treatment seeking human subjects meeting diagnostic criteria for cocaine use disorder will sample doses of intravenous cocaine (0, 10 and 30 mg/70 kg) in experimental sessions after 3 days of maintenance on oral zolmitriptan (0, 2.5, 5 and 10 mg). A placebo-controlled, double-blind, within-subjects design will be used such that all subjects experience all dose conditions in random order. The study will require an approximately 1-month admission to our inpatient unit. After sampling a cocaine dose, subjects will make nine choices between that dose and an alternative reinforcer (US$6.00) on a concurrent progressive-ratio choice task that was developed and validated in our laboratory. A battery of subjective drug-effect measures and tasks that assess distinct domains of impulsivity will be completed during the same experimental sessions in which cocaine choice is assessed. The research proposed here will directly translate findings from preclinical research and provide the initial clinical evidence that 5-HT1b activation, achieved through administration of zolmitriptan, reduces the reinforcing and other abuse-related effects of cocaine, as well as cocaine-associated impulsivity. This study will also provide basic science information about the serotonergic mechanisms underlying the pharmacodynamic effects of cocaine in humans. As such, the outcomes will advance our understanding of the clinical neurobiology of cocaine addiction.
摘要

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)

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William Walton Stoops其他文献

Acute inhibitory control training in cocaine users
  • DOI:
    10.1016/j.drugalcdep.2016.08.029
  • 发表时间:
    2017-02-01
  • 期刊:
  • 影响因子:
  • 作者:
    Joseph L. Alcorn;Erika Pike;Joshua A. Lile;William Walton Stoops;Craig R. Rush
  • 通讯作者:
    Craig R. Rush
The influence of buspirone maintenance on the pharmacodynamic effects of methamphetamine
  • DOI:
    10.1016/j.drugalcdep.2016.08.481
  • 发表时间:
    2017-02-01
  • 期刊:
  • 影响因子:
  • 作者:
    Anna R. Reynolds;William Walton Stoops;Joshua A. Lile;Craig R. Rush
  • 通讯作者:
    Craig R. Rush

William Walton Stoops的其他文献

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{{ truncateString('William Walton Stoops', 18)}}的其他基金

Scientific Conferences for The College on Problems of Drug Dependence (CPDD)
药物依赖问题学院科学会议(CPDD)
  • 批准号:
    10377420
  • 财政年份:
    2021
  • 资助金额:
    $ 66.01万
  • 项目类别:
Scientific Conferences for The College on Problems of Drug Dependence (CPDD)
药物依赖问题学院科学会议(CPDD)
  • 批准号:
    10230873
  • 财政年份:
    2021
  • 资助金额:
    $ 66.01万
  • 项目类别:
Influence of Orexin Antagonism on Motivation for Cocaine
食欲素拮抗作用对可卡因动机的影响
  • 批准号:
    9765804
  • 财政年份:
    2019
  • 资助金额:
    $ 66.01万
  • 项目类别:
Influence of Orexin Antagonism on Motivation for Cocaine
食欲素拮抗作用对可卡因动机的影响
  • 批准号:
    9919535
  • 财政年份:
    2019
  • 资助金额:
    $ 66.01万
  • 项目类别:
Cardiovascular, Immune and Psychosocial Benefits of Reduced Cocaine Use
减少可卡因使用对心血管、免疫和社会心理的益处
  • 批准号:
    9469852
  • 财政年份:
    2017
  • 资助金额:
    $ 66.01万
  • 项目类别:
Selective Monoamine Release as a Treatment for Cocaine Use Disorders
选择性单胺释放作为可卡因使用障碍的治疗
  • 批准号:
    8753852
  • 财政年份:
    2014
  • 资助金额:
    $ 66.01万
  • 项目类别:
Motivation for Cocaine and Non-Drug Reinforcers: Targeting Glutamate Homeostasis
可卡因和非药物强化剂的动机:以谷氨酸稳态为目标
  • 批准号:
    8633724
  • 财政年份:
    2014
  • 资助金额:
    $ 66.01万
  • 项目类别:
A Human Laboratory Study to Investigate Buspirone for Cocaine Use Disorders
调查丁螺环酮治疗可卡因使用障碍的人体实验室研究
  • 批准号:
    8334921
  • 财政年份:
    2012
  • 资助金额:
    $ 66.01万
  • 项目类别:
A Human Laboratory Study to Investigate Buspirone for Cocaine Use Disorders
调查丁螺环酮治疗可卡因使用障碍的人体实验室研究
  • 批准号:
    8518284
  • 财政年份:
    2012
  • 资助金额:
    $ 66.01万
  • 项目类别:
Neuropharmacology of Tramadol: Clinical Efficacy and Abuse Potential
曲马多的神经药理学:临床疗效和滥用潜力
  • 批准号:
    7729609
  • 财政年份:
    2009
  • 资助金额:
    $ 66.01万
  • 项目类别:
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