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: 7919322
• 负责人: Donita L Robinson
• 金额: $ 31.14万
• 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/7919322
• 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（由申请人提供）：酒精中毒是一种慢性疾病，通常跨越几十年。习惯形成的学习过程可能有助于持续饮酒，并使行为具有抵抗力的变化。习惯（由有条件提示和独立于结果的行为）与目标指导行为（取决于结果或药物的行为）的程度可能会影响饮酒的易感性。大鼠的操作调节范例可以产生强大的目标定向或习惯行为，可以模拟习惯对饮酒的贡献，并可以在这些行为期间直接测量大脑功能。背侧纹状体（DMS）是目标指导行为的基础，而背外侧纹状体（DLS）对于习惯形成至关重要，并且两个地区都参与复发的动物模型。多巴胺的输入对于提示和药物之间的关联至关重要，并且对突触可塑性，神经元活性和行为具有深远的区域特异性作用。提示习惯中的临界多巴胺信号可能是多巴胺（或瞬变）的快速变化，这些变化可能会响应显着刺激而发生，并且只能通过快速扫描环状伏安法测量。此外，背纹状体中的中刺神经元可以通过短期发射速率变化来编码与奖励相关的提示和作用，这可能是多巴胺依赖的。该提案将检验总体假设，即DMS与DM相比，多巴胺释放和持续的神经元活性不同，而DMS在目标指导的酒精加强期间优先活跃，而DLS在惯性的酒精增强过程中优先活跃，并且在习惯性酒精加强过程中优先活跃。我们将在大鼠中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瞬变，并在多电极阵列处进行细胞外记录，以评估MSN的集合活动。此外，我们将在目标和习惯性饮酒（目标1和2）以及类似复发的行为（目标3和4）的过程中将化学和生理测量的组合（目标3和4）组合在一起，以提供迄今为止最完整的背景。与酒精相关习惯形成的纹状体编码。机械研究将研究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。这些创新研究产生的数据将提供有关背侧纹状体如何差异编码目标指导与习惯性饮酒的重要信息。总体而言，这些研究有可能识别新型机制，习惯性饮酒会导致大脑和行为过程的变化，这对于对酒精滥用和酒精中毒的发展和治疗至关重要。 公共卫生相关性：习惯性饮酒和提示引起的复发是酒精中毒的主要因素。我们将在习惯性饮酒和提示引起的复发的大鼠模型中检查多巴胺释放和神经活动。