Cue-triggered reward seeking

描述（申请人提供）：本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，药物线索可以导致人类成瘾者重新陷入强迫性药物寻求行为，即使在长期戒断药物使用之后。我们称这种现象为线索触发的“想要”奖励，这是由于奖励显著性过度归因于奖励条件刺激。 我们建立了一个研究线索触发的激励动机的神经行为机制的大鼠行为模型--纯条件激励范式。 使用一种天然的奖励，蔗糖，允许暴露的激励显着性“想要”的机制，而不会受到药物戒断的污染。我们证明，微量注射安非他明到丘脑核特别增强线索触发的“想要”蔗糖奖励超过400%。我们的行为模型排除了其他解释的提示效应（条件强化，联想习惯等）的中脑边缘调解。我们还发现，致敏相关的变化所造成的前安非他明管理导致持续增加线索触发的“想要”的奖励所预测的激励敏化假说。 在拟议的研究中，我们将调查特定的多巴胺受体在线索触发的“想要”中的作用（使用特定的多巴胺激动剂和拮抗剂的显微注射）。 我们还将澄清的神经解剖学作用的壳与核心（在显微注射映射实验和使用兴奋性毒性病变）。 重要的是，我们将评估增加对蔗糖的线索触发的“想要"的中脑边缘激活是否也增加对蔗糖的”喜欢“（使用蔗糖”喜欢“的味觉反应性测量）。 最后，我们将测试的持续时间的敏化相关的增加线索触发的“想要”所造成的先前可卡因，安非他明或吗啡管理，并将调查的相互作用的敏化与中脑边缘激活药物显微注射。这些研究将有助于阐明自然线索触发“渴求”的基本机制，并有助于理解人类药物成瘾中线索触发复吸的机制。

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.