Cue-triggered reward seeking

提示触发奖励寻求

• 批准号: 7284318
• 负责人: Kent C. Berridge
• 金额: $ 24.42万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7284318
• 关键词: Cue; triggered; reward; seeking

DESCRIPTION (provided by applicant): This project investigates biopsychological mechanisms of how reward cues trigger intense seeking behavior for their reward. For example, drug cues can cause human addicts to relapse into compulsive drug seeking behavior, even after long abstinence from drug use. We call this phenomenon, cue-triggered 'wanting' of reward, due to excessive attribution of incentive salience to the reward conditioned stimulus. We have developed a behavioral model to study the neurobehavioral mechanism of cue-triggered incentive motivation in rats, the pure conditioned incentive paradigm. Using a natural reward, sucrose, allows exposure of incentive salience 'wanting' mechanisms without contamination by drug withdrawal. We demonstrated that microinjection of amphetamine into nucleus accumbens specifically enhanced cue-triggered 'wanting' for sucrose reward by over 400%. Our behavioral model ruled out alternative explanations for mesolimbic mediation of cue effects (conditioned reinforcement, associative habits, etc.). We have also found that sensitization-related changes caused by prior amphetamine administration leads to a persistent increase in cue-triggered 'wanting' for reward as predicted by the incentive-sensitization hypothesis. In the proposed studies, we will investigate the role of specific dopamine receptors in cue-triggered 'wanting' (using microinjection of specific dopamine agonists and antagonists). We will also clarify the neuroanatomical roles of accumbens shell versus core (in a microinjection mapping experiment and using excitotoxic lesions). Importantly, we will assess whether mesolimbic activation that increase cue-triggered 'wanting' for sucrose also increases 'liking' for sucrose (using the taste reactivity measure of sucrose 'liking'). Finally, we will test the duration of the sensitization-related increase in cue-triggered 'wanting' caused by prior cocaine, amphetamine or morphine administration, and will investigate the interaction of sensitization with mesolimbic activation by drug microinjection. These studies will clarify basic mechanisms of natural cue-triggered 'wanting', and will be useful in understanding mechanisms of cue-triggered relapse in human drug addiction.

描述（由申请人提供）：该项目调查了奖励提示如何触发强烈寻求行为以获得奖励的生物心理学机制。 例如，即使经过长期禁欲使用毒品，毒品提示也会导致人类成瘾者复发到强迫性毒品的行为中。我们称这种现象称为提示触发的“缺乏奖励”，这是因为激励刺激的过多归因于奖励有条件的刺激。 我们已经开发了一种行为模型来研究大鼠提示激励动机的神经行为机制，即纯条件的激励范式。 使用自然奖励，蔗糖可以使激励显着性“想要”机制暴露而不会被药物戒烟污染。我们证明，苯丙胺对伏隔核的微注射特异性增强了提示触发的“想要”，以增加超过400％的蔗糖奖励。我们的行为模型排除了提示效应中溶胶介导的替代解释（条件增强，联想习惯等）。我们还发现，由先前的苯丙胺给药引起的与敏化相关的变化导致提示触发的“渴望”持续增加，以获得奖励假设所预测的奖励。 在拟议的研究中，我们将研究特定多巴胺受体在提示触发的“渴望”中的作用（使用特定多巴胺激动剂和拮抗剂的显微注射）。 我们还将阐明伏隔壳与核心的神经解剖学作用（在微注射映射实验和使用兴奋性病变中）。 重要的是，我们将评估增加提示提示触发的蔗糖“渴望”的中溶液激活也增加了蔗糖的“喜欢”（使用蔗糖“喜欢”的味觉反应性测量）。 最后，我们将测试由先前可卡因，苯丙胺或吗啡给药引起的提示触发的“欲望”的敏感性增加的持续时间，并将研究通过药物微分注射的敏化敏化与中溶液激活的相互作用。这些研究将阐明自然提示触发的“欲望”的基本机制，并有助于理解人类药物成瘾中提示触发的复发机制。