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）：该项目研究奖励线索如何触发强烈寻求奖励行为的生物心理学机制。 例如，药物提示可能会导致人类成瘾者重新陷入强迫性的药物寻求行为，即使在长期戒毒之后也是如此。我们将这种现象称为提示触发的“想要”奖励，这是由于奖励的显着性过度归因于奖励条件刺激。 我们开发了一种行为模型来研究大鼠提示触发激励动机的神经行为机制，即纯条件激励范式。 使用自然奖励蔗糖可以暴露激励显着性“想要”机制，而不会受到药物戒断的污染。我们证明，将安非他明显微注射到伏隔核中，可以将提示触发的对蔗糖奖励的“渴望”增强 400% 以上。我们的行为模型排除了中脑边缘调节提示效应的其他解释（条件强化、联想习惯等）。我们还发现，先前使用安非他明引起的与敏化相关的变化会导致提示触发的对奖励​​的“渴望”持续增加，正如激励敏化假说所预测的那样。 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“想要”中的作用（使用特定多巴胺激动剂和拮抗剂的显微注射）。 我们还将阐明伏隔核壳与核心的神经解剖学作用（在显微注射映射实验中并使用兴奋性毒性损伤）。 重要的是，我们将评估增加提示触发的对蔗糖“想要”的中脑边缘激活是否也会增加对蔗糖的“喜欢”（使用蔗糖“喜欢”的味觉反应性测量）。 最后，我们将测试由先前给予可卡因、安非他明或吗啡引起的提示触发“想要”的致敏相关增加的持续时间，并将通过药物显微注射研究致敏与中脑边缘激活的相互作用。这些研究将阐明自然线索触发的“想要”的基本机制，并将有助于理解线索触发的人类毒瘾复发的机制。