Cue-triggered reward seeking

描述(由申请者提供)：这个项目调查了奖励线索如何引发强烈的寻求奖励行为的生物心理学机制。例如，毒品线索可能会导致人类吸毒者重新陷入强迫寻求毒品的行为，即使在长期戒毒后也是如此。我们将这种现象称为线索触发的奖赏想要现象，这是由于对奖赏条件刺激的激励显著过度归因。我们开发了一个行为模型来研究线索触发的大鼠激励动机的神经行为机制，这是一种纯条件激励范式。使用一种自然的奖励--蔗糖，可以在不被停药污染的情况下，暴露出激励突出的“想要”的机制。我们证明，在伏隔核内微量注射苯丙胺，可以使线索触发的对蔗糖奖赏的“渴求”增加400%以上。我们的行为模型排除了对线索效应(条件性强化、联想习惯等)的中间边缘调节的其他解释。我们还发现，如激励敏化假说所预测的那样，先前服用苯丙胺引起的敏化相关变化会导致线索触发的对奖励的“渴望”持续增加。在拟议的研究中，我们将研究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微量注射)。我们还将阐明伏隔核外壳与核心的神经解剖学作用(在显微注射标测实验中和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的“想要”是否也增加了对蔗糖的“喜欢”(使用蔗糖的味道反应性衡量标准)。最后，我们将测试由先前注射可卡因、安非他明或吗啡引起的线索触发的“想要”的敏化相关增加的持续时间，并将通过药物微量注射来研究敏化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，并将有助于理解人类药物成瘾中线索触发的复发机制。

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.