Habits and cues in alcohol drinking: Dynamic striatal activity

饮酒的习惯和线索：动态纹状体活动

• 批准号: 7692339
• 负责人: Donita L Robinson
• 金额: $ 30.02万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7692339
• 关键词: Alcohol consumption; Alcohol dependence; Alcoholism; Alcohols; Animal Model; Ants; Area; Arts; Behavior; Behavioral; Brain; Chemicals; Chronic Disease; Code; Corpus striatum structure; Cues; Data; Dopa; Dopamine; Dorsal; Event; Extinction (Psychology); Goals; Habits; Human; Imagery; Learning; Measurement; Measures; Microdialysis; Mining; Modeling; Monitor; Neurons; Nucleus Accumbens; Operant Conditioning; Outcome; Pattern; Pharmaceutical Preparations; Physiological; Predisposition; Process; Rattus; Reinforcement Schedule; Relapse; Relative (related person); Reporting; Resistance; Rewards; Role; Scanning; Schedule; Self Administration; Series; Signal Transduction; Stimulus; Synaptic plasticity; Techniques; Testing; Time; Training; alcohol abuse therapy; alcohol cue; alcohol reinforcement; alcohol seeking behavior; base; drinking; drugged driving; extracellular; in vivo; information processing; innovation; insight; neuroadaptation; neurochemistry; novel; prevent; public health relevance; receptor; reinforcer; relating to nervous system; research study; response; therapy development

DESCRIPTION (provided by applicant): Alcoholism is a chronic disorder, typically spanning several decades. The learning processes underlying habit formation may contribute to continued alcohol drinking and render the behavior resistant to change. The degree to which habits (actions driven by conditioned cues and independent of outcome) versus goal-directed behaviors (actions dependent on the outcome or drug) drive alcohol drinking may influence susceptibility to relapse. Operant conditioning paradigms in rats, which can produce robust goal-directed or habitual behavior, can model the contribution of habit to alcohol drinking and allow direct measurement of brain function during these behaviors. The dorsomedial striatum (DMS) underlies goal-directed behavior while the dorsolateral striatum (DLS) is crucial for habit formation, and both areas are involved in animal models of relapse. Dopamine input is essential to the association between cues and drugs, and has profound and region-specific effects on synaptic plasticity, neuronal activity and behavior. The critical dopamine signal in cue-action habits may be fast changes in dopamine (or transients) that can occur in response to salient stimuli and that can only be measured with fast scan cyclic voltammetry. In addition, medium spiny neurons in the dorsal striatum can encode reward-related cues and actions by short-term changes in firing rates, which may be dopamine- dependent. This proposal will test the overall hypothesis that subsecond dopamine release and ongoing neuronal activity differ in DMS versus DLS, with the DMS preferentially active during goal-directed alcohol reinforcement, and the DLS preferentially active during habitual alcohol reinforcement and cue-induced relapse. We will use state-of-the-art, real-time recording techniques in rats: fast scan cyclic voltammetry to reveal dopamine transients, and extracellular recording at multielectrode arrays to evaluate ensemble activity of MSNs. Moreover, we will make this combination of chemical and physiological measurements during goal- directed and habitual alcohol drinking (Aims 1 and 2) as well as relapse-like behavior (Aims 3 and 4), to provide the most complete picture to date of dorsal striatal encoding of alcohol-related habit formation. Mechanistic studies will investigate the functional role of dopamine release in the physiological events associated with habitual drinking and relapse. The data resulting from these innovative studies will provide important information about how the dorsal striatum differentially encodes goal-directed versus habitual alcohol drinking. Overall, these studies have the potential to identify novel mechanisms by which habitual alcohol drinking leads to changes in brain and behavioral processes that are of fundamental importance to both the development and treatment of alcohol abuse and alcoholism. PUBLIC HEALTH RELEVANCE: Habitual alcohol drinking and cue-induced relapse are major factors to alcoholism. We will examine dopamine release and neural activity in rat models of habitual alcohol drinking and cue-induced relapse.

描述(申请人提供)：酒精中毒是一种慢性疾病，通常持续数十年。习惯形成背后的学习过程可能会导致持续饮酒，并使行为抵抗改变。习惯(由条件线索驱动的行为，与结果无关)与目标导向行为(依赖于结果或药物的行为)驱使饮酒的程度可能会影响复发的易感性。大鼠的操作条件反射范式可以产生强大的目标导向或习惯性行为，可以模拟习惯对饮酒的贡献，并允许在这些行为期间直接测量大脑功能。背内侧纹状体(DMS)是目标导向行为的基础，背外侧纹状体(DLS)是形成习惯的关键区域，这两个区域都参与了复吸的动物模型。多巴胺的输入对线索和药物之间的联系是必不可少的，并且对突触可塑性、神经元活动和行为具有深远的和区域特异性的影响。提示动作习惯中的关键多巴胺信号可能是多巴胺(或瞬间)的快速变化，这种变化可能发生在对显著刺激的反应中，并且只能用快速扫描循环伏安法来测量。此外，背侧纹状体中的中棘神经元可以通过短期改变放电频率来编码与奖励相关的暗示和行动，这可能是多巴胺依赖的。这一建议将检验总体假设，即DMS和DLS的亚秒多巴胺释放和持续的神经元活动不同，DMS在目标定向酒精强化期间优先激活，而DLS在习惯性酒精强化和线索诱导的复发期间优先激活。我们将在大鼠身上使用最先进的实时记录技术：快速扫描循环伏安法来揭示多巴胺的瞬变，以及在多电极阵列上的细胞外记录来评估MSN的整体活性。此外，我们将在目标导向和习惯性饮酒(目标1和2)以及类似复发的行为(目标3和4)中进行这种化学和生理测量的组合，以提供迄今为止与酒精相关的习惯形成的背侧纹状体编码的最完整图景。机制研究将调查多巴胺释放在与习惯性饮酒和复发相关的生理事件中的功能作用。来自这些创新研究的数据将提供关于背侧纹状体如何差异编码目标导向型饮酒和习惯性饮酒的重要信息。总体而言，这些研究有可能确定习惯性饮酒导致大脑和行为过程变化的新机制，这些变化对酒精滥用和酒精中毒的发展和治疗都是至关重要的。 公共卫生相关性：习惯性饮酒和线索诱发的复发是导致酒精中毒的主要因素。我们将在习惯性饮酒和线索诱导复发的大鼠模型中检测多巴胺释放和神经活动。