Cognitive Function in Alcohol Dependence and Protracted Withdrawal

酒精依赖和长期戒断的认知功能

基本信息

  • 批准号:
    9303764
  • 负责人:
  • 金额:
    $ 38.7万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-07-15 至 2019-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Impaired cognitive processing is a hallmark of addiction. Deficits in inhibitory control (impulsive action), poor evaluation of consequences (impulsive choice) and ineffective reversal of compulsive or habitual behaviors (cognitive flexibility) can propel continued drug use despite adverse consequences. A persistent question in alcohol research regards the relative influence of pre-existing cognitive disruptions that confe susceptibility to problem drinking versus the induction of cognitive impairment related to cortical damage induced by repeated alcohol intoxication and withdrawal. In this regard animal models can provide important insight into the etiology of alcohol-induced cognitive impairment and can provide a platform for mechanistic studies and rapid pharmacotherapy screening. Using behavioral paradigms analogous to clinically employed tasks we have gathered preliminary evidence of significant increases in impulsive action and impulsive choice behaviors that emerge in rats during protracted withdrawal from long-term intermittent alcohol consumption. These cognitive impairments persist for several weeks, and can be ameliorated by a pharmacological manipulation known to improve cognitive function in human alcoholics. Based on these findings and knowledge of the neural mechanisms governing these behaviors in rats we hypothesize that withdrawal-associated dysregulation of monoamine and amino acid signaling in frontal cortical regions contributes to increased impulsivity and deficient cognitive flexibility during protracted alcohol withdrawal. This hypothesis will be tested through three Specific Aims. Aim 1 will characterize the emergence, nature and persistence of cognitive disruption during protracted alcohol withdrawal. Different facets of impulsive action will be explored using a novel 5-Choice Continuous Performance Task (5C-CPT) and the Stop Signal Reaction Time task (SSRT). Impulsive choice behavior will be indexed using the Delay Discount Test, and cognitive flexibility will be assessed using an operant spatial reversal learning task. The experiments in Aim 2 will employ in vivo microdialysis and biochemical approaches to characterize monoamine, and amino acid function in the orbitofrontal and medial prefrontal cortices during protracted alcohol withdrawal. Aim 3 will evaluate the efficacy of pharmacologic agents for ameliorating withdrawal-associated increases in impulsive action and impulsive choice.
描述(由申请人提供):认知处理受损是成瘾的标志。抑制控制的缺陷(冲动行为),对后果的不良评估(冲动选择)和对强迫或习惯性行为的无效逆转(认知灵活性)可以推动持续使用药物,尽管有不良后果。酒精研究中一个持续存在的问题是,导致饮酒问题易感性的预先存在的认知中断与诱发与皮质相关的认知损伤的相对影响

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:
    $ 38.7万
  • 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:
    $ 38.7万
  • 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:
    $ 38.7万
  • 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:
    $ 38.7万
  • 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:
    $ 38.7万
  • 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:
    $ 38.7万
  • 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:
    $ 38.7万
  • 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:
    $ 38.7万
  • 项目类别:
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
  • 批准号:
    9110011
  • 财政年份:
    2016
  • 资助金额:
    $ 38.7万
  • 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:
    8484812
  • 财政年份:
    2012
  • 资助金额:
    $ 38.7万
  • 项目类别:

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适应性行为和反应模式中乙酰胆碱活性的时空动态
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乙酰胆碱的生物学意义及其在食物资源中的含量研究
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  • 财政年份:
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纹状体多巴胺释放的烟碱乙酰胆碱受体差异调节是药物获取率个体差异的机制
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烟碱乙酰胆碱受体门控和毒素抑制的结构基础
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烟碱乙酰胆碱受体调节可卡因奖赏的机制
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