The role of phasic dopamine release in cue-evoked motivated behaviors

阶段性多巴胺释放在提示诱发的动机行为中的作用

• 批准号: 7806792
• 负责人: Matthew J. Wanat
• 金额: $ 5.01万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7806792
• 关键词: Address; Affect; Attenuated; Behavior; Behavioral; Behavioral Paradigm; Cocaine; Cues; Disease; Dopamine; Drug Addiction; Drug Delivery Systems; Emotional; Event; Food; Food deprivation (experimental); Foundations; Goals; Infusion procedures; Length; Measures; Motivation; Nucleus Accumbens; Output; Pattern; Pharmaceutical Preparations; Psychological reinforcement; Punishment; Rattus; Reinforcement Schedule; Research; Rodent; Role; Satiation; Scanning; Signal Transduction; Societies; Withdrawal; addiction; cocaine exposure; dopamine system; dopaminergic neuron; drug craving; drug of abuse; economic impact; experience; feeding; food consumption; genetic manipulation; improved; motivated behavior; neural circuit; neurochemistry; neuromechanism; reinforcer

DESCRIPTION (provided by applicant): Drug addiction is a disease with a devastating emotional and economic impact on society, which in turn has stimulated research that seeks to identify the neural mechanisms involved with addiction. Many lines of evidence suggest that drug addiction alters the motivation to pursue drugs. In particular, drug-related cues can promote motivated drug seeking through activation of the mesocorticolimbic dopamine system. However, little is known regarding how reinforcer-associated cues affect dopamine release in the nucleus accumbens (NAcc) in behaviors specifically examining motivation. Identifying the role of dopamine release to cues associated with reinforcer availability during motivated behaviors will improve our understanding of the neurochemical signals involved with motivation, and will also highlight specific dopamine release patterns that when blocked, could potentially attenuate how drug-related cues promote drug seeking. Motivation is often assessed in operant tasks that utilize progressive ratio (PR) reinforcement schedules. During PR reinforcement schedules, the net value of the reinforcer is diminished as the operant requirement to obtain a reinforcer increases on subsequent trials until operant responding ceases, which is the 'break- point' and is a measure of motivational effort one will expend to obtain a reinforcer. While dopamine release in the NAcc is involved with motivated operant output, surprisingly little is known regarding the temporal release patterns of dopamine during motivated behaviors. Phasic (sub-second) dopamine release in the NAcc precedes the initiation of goal-directed actions, which suggests that phasic dopamine release is involved with motivated behaviors. However, it is unknown how dopamine is released to cues associated with reinforcer availability in behavioral paradigms explicitly assessing motivation. In this regard, this proposal addresses this experimental question by utilizing voltammetry to determine the role of phasic, sub- second dopamine release in the NAcc to cues predicting reinforcer availability in rats during an operant task with a PR reinforcement schedule for either natural reinforcers (Aim 1) or drugs of abuse (Aim 2). A critical component of drug addiction is an enhanced motivation to purse drugs, which involves the actions of dopamine, although it is unknown how dopamine is released during behaviors specifically examining motivation. This proposal examines the role of sub-second dopamine release in the motivated pursuit of both natural (food) and drug (cocaine) reinforcers, which will enhance our understanding of the neurochemical signals involved with motivated behaviors, and will also highlight specific dopamine release patterns that when blocked, could reduce the motivation to pursue drugs.

描述（由申请人提供）：吸毒是一种对社会产生毁灭性情感和经济影响的疾病，这反过来刺激了研究，旨在识别与成瘾有关的神经机制。许多证据表明，吸毒成瘾改变了追求药物的动机。特别是，与药物相关的提示可以通过激活中皮质糖多巴胺系统来促进积极的药物寻求。然而，关于增强剂相关的提示如何影响伏隔核（NACC）在专门研究动机的行为中，知之甚少。确定多巴胺释放在动机行为过程中与增强剂可用性相关的提示的作用将提高我们对动机涉及的神经化学信号的理解，并且还将突出显示特定的多巴胺释放模式。 通常在利用渐进式比率（PR）增强时间表的操作任务中评估动机。在公关增强计划期间，随着操作者要求获得加强剂的要求，钢筋的净值会降低，直到操作者的响应停止为止，这是“突破点”，这是对激励努力的衡量，这是一项衡量的量增强器。尽管NACC中的多巴胺释放涉及动机的运营产量，但令人惊讶的是，关于动机行为过程中多巴胺的时间释放模式知之甚少。 NACC中的阶段（次秒）多巴胺释放在目标指导作用的启动之前，这表明阶段性多巴胺释放与动机行为有关。但是，尚不清楚多巴胺如何释放出与行为范式中的增强剂可用性相关的提示，以明确评估动机。在这方面，该提案通过利用伏安法来确定NACC中阶段，第二次多巴胺释放的作用，以提示在操作任务中以PR增强进度来预测大鼠的增强剂的可用性（AIM AIM AIM（AIM）） 1）或滥用药物（目标2）。 药物成瘾的一个关键组成部分是涉及多巴胺的作用的增强动力，尽管在行为期间如何释放多巴胺是如何专门研究动机的。该提案研究了亚秒多巴胺释放在动机追求天然（食物）和药物（可卡因）增强剂中的作用，这将增强我们对与动机行为相关的神经化学信号的理解，还将突出显示特定的多巴胺释放模式当被阻止时，可以减少追求毒品的动力。