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
- 来源:
- 关键词:AbstinenceAcetylcholineAcetylcysteineAlcohol abuseAlcohol consumptionAlcohol dependenceAlcohol withdrawal syndromeAlcoholic IntoxicationAlcoholismAlcoholsAmino AcidsAnimal ModelBehaviorBehavioralBehavioral ParadigmBehavioral inhibitionBiochemicalChoice BehaviorChronicClinicalCognitiveComplementConsumptionDataDeltastabDoseDrug usageEtiologyEvaluationFunctional disorderGlutamatesHeavy DrinkingHumanImpaired cognitionImpairmentImpulsivityIndividualInvestigationKnowledgeMeasuresMedialMediatingMessenger RNAMicrodialysisNatureNeurophysiology - biologic functionNeurotransmittersPerformancePharmaceutical PreparationsPharmacologyPharmacotherapyPredispositionPrefrontal CortexRattusReaction TimeReversal LearningRodent ModelSamplingSerotoninSignal TransductionSpeedTask PerformancesTestingTherapeuticTreatment EfficacyWestern BlottingWithdrawaladdictionadverse outcomealcohol researchatomoxetinebasecognitive functiondesigndiscountdiscountingdrinkingexperimental studyextracellularflexibilitygabapentingamma-Aminobutyric Acidimprovedin vivoindexinginsightlearned behaviormonoamineneurochemistryneuromechanismneurophysiologynovelperformance testspre-clinicalproblem drinkerpublic health relevancequetiapinereceptorreceptor expressionresponsescreening
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。抑制控制缺陷(冲动行为)、对后果评价不佳(冲动选择)以及强迫或习惯行为(认知灵活性)的无效逆转可能会推动继续吸毒,尽管会产生不良后果。酒精研究中一个持续存在的问题是,先前存在的认知障碍(导致对问题饮酒的易感性)与诱发与皮质相关的认知障碍的相对影响
反复酒精中毒和戒断引起的损害。在这方面,动物模型可以为酒精引起的认知障碍的病因学提供重要的见解,并可以为机制研究和快速药物治疗筛选提供平台。使用类似于临床任务的行为范式,我们收集了初步证据,表明大鼠在长期间歇性饮酒的长期戒断过程中出现的冲动行为和冲动选择行为显着增加。这些认知障碍会持续数周,并且可以通过已知可改善人类酗酒者认知功能的药物操作来改善。基于这些发现和对控制大鼠这些行为的神经机制的了解,我们假设与戒断相关的额叶皮质区单胺和氨基酸信号传导失调导致长期酒精戒断期间冲动性增加和认知灵活性不足。这一假设将通过三个具体目标进行检验。目标 1 将描述长期戒酒期间认知障碍的出现、性质和持续性。将使用新颖的 5 选择连续性能任务 (5C-CPT) 和停止信号反应时间任务 (SSRT) 来探索冲动行为的不同方面。冲动选择行为将使用延迟贴现测试进行索引,认知灵活性将使用操作性空间反转学习任务进行评估。目标 2 中的实验将采用体内微透析和生化方法来表征长期戒酒期间眶额叶和内侧前额叶皮质中的单胺和氨基酸功能。目标 3 将评估药物对于改善戒断相关的冲动行为和冲动选择增加的功效。
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:
10671018 - 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.
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- 批准号:
10447503 - 财政年份:2022
- 资助金额:
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Drug targeting the dynamics of opioid systems in alcohol dependence
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针对酒精依赖中阿片类药物系统动态的药物
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10032660 - 财政年份:2020
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针对酒精依赖中阿片类药物系统动态的药物
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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
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10436851 - 财政年份:2018
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10200612 - 财政年份:2018
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