Dysregulation of thalamic hypocretin transmission following ethanol dependence

乙醇依赖后丘脑下丘脑分泌素传输失调

基本信息

  • 批准号:
    9110011
  • 负责人:
  • 金额:
    $ 22.86万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-06-15 至 2018-05-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): The hypocretin (Hcrt) system has long been known to regulate a wide range of physiological processes, including feeding, energy metabolism, and arousal. More recently, concordant observations have demonstrated an important role for Hcrt in the reinforcing properties of most drugs of abuse. Accordingly, Hcrt neurons, which predominantly arise from the lateral hypothalamus (LH), project to brain structures implicated in the regulation of arousal, stress, and reward. Although Hcrt neurons have been shown to massively project to the paraventricular nucleus of the thalamus (PVT), recent evidence suggests that the PVT may be a key relay of Hcrt-coded reward-related communication between the LH and both the ventral and dorsal striatum. While this thalamic region was not thought to be part of "drug addiction circuitry," an increasing amount of evidence indicates that the PVT-particularly Hcrt transmission in the PVT-is implicated in the modulation of reward function in general and several aspects of drug-directed behaviors in particular. Importantly, findings from our laboratory demonstrated selective activation of the PVT during ethanol seeking, and our preliminary data suggest that a history of ethanol dependence produces a downregulation of Hcrt in the LH and upregulation of Hcrtr1 (encoding Hcrt receptor 1) in the PVT. This proposal is designed to study the neurobiological basis of chronic vulnerability to relapse by focusing on Hcrt transmission in the PVT as a novel neural substrate that may be responsible for the compulsive nature of ethanol seeking. Specifically, this proposal will (i) establish the role of Hcrt transmission in the PVT in ethanol-seeking behavior and (ii) test the hypothesis that knocking down Hcrt using local gene silencing in the LH in nondependent rats will mimic the phenotype of postdependent rats. Overall, the planned experiments will provide novel insights into the specific involvement of LH→PVT Hcrt transmission in alcohol-seeking behavior and will likely highlight a previously unrecognized neurotransmission system in the etiology of compulsive alcohol seeking during abstinence and justify targeting the hyprocretin system for alcoholism and relapse prevention.


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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Remi Martin-Fardon其他文献

Remi Martin-Fardon的其他文献

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{{ truncateString('Remi Martin-Fardon', 18)}}的其他基金

Cocaine-motivated behaviors: development of novel viral-based strategies to target orexinergic input to the infralimbic cortex.
可卡因驱动的行为:开发基于病毒的新型策略,将食欲素输入瞄准边缘下皮层。
  • 批准号:
    10447503
  • 财政年份:
    2022
  • 资助金额:
    $ 22.86万
  • 项目类别:
Cocaine-motivated behaviors: development of novel viral-based strategies to target orexinergic input to the infralimbic cortex.
可卡因驱动的行为:开发基于病毒的新型策略,将食欲素输入瞄准边缘下皮层。
  • 批准号:
    10671018
  • 财政年份:
    2022
  • 资助金额:
    $ 22.86万
  • 项目类别:
Drug targeting the dynamics of opioid systems in alcohol dependence
针对酒精依赖中阿片类药物系统动态的药物
  • 批准号:
    10443881
  • 财政年份:
    2020
  • 资助金额:
    $ 22.86万
  • 项目类别:
Drug targeting the dynamics of opioid systems in alcohol dependence
针对酒精依赖中阿片类药物系统动态的药物
  • 批准号:
    10032660
  • 财政年份:
    2020
  • 资助金额:
    $ 22.86万
  • 项目类别:
Drug targeting the dynamics of opioid systems in alcohol dependence
针对酒精依赖中阿片类药物系统动态的药物
  • 批准号:
    10662302
  • 财政年份:
    2020
  • 资助金额:
    $ 22.86万
  • 项目类别:
Drug targeting the dynamics of opioid systems in alcohol dependence
针对酒精依赖中阿片类药物系统动态的药物
  • 批准号:
    10266772
  • 财政年份:
    2020
  • 资助金额:
    $ 22.86万
  • 项目类别:
Pivotal role of thalamic hypocretin transmission during EtOH seeking and relapse
丘脑下丘脑分泌素传输在乙醇寻找和复发过程中的关键作用
  • 批准号:
    10436851
  • 财政年份:
    2018
  • 资助金额:
    $ 22.86万
  • 项目类别:
Pivotal role of thalamic hypocretin transmission during EtOH seeking and relapse
丘脑下丘脑分泌素传输在乙醇寻找和复发过程中的关键作用
  • 批准号:
    10200612
  • 财政年份:
    2018
  • 资助金额:
    $ 22.86万
  • 项目类别:
Cognitive Function in Alcohol Dependence and Protracted Withdrawal
酒精依赖和长期戒断的认知功能
  • 批准号:
    9303764
  • 财政年份:
    2013
  • 资助金额:
    $ 22.86万
  • 项目类别:
Role of Orexin/Hypocretin in cocaine-seeking behavior
食欲素/下丘脑分泌素在可卡因寻求行为中的作用
  • 批准号:
    8397500
  • 财政年份:
    2012
  • 资助金额:
    $ 22.86万
  • 项目类别:

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糖皮质激素受体介导的 mRNA 衰减在酒精依赖中的作用
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