Incubation of Craving: Neural Substrates (competitive renewal)

描述（由申请人提供）：高复发率是药物和食物成瘾的特征。复发之前通常有强烈渴望的主观报告，这些渴望可以由药物或食物配对刺激引起。老鼠会按下一个杠杆，以呈现一种刺激复合体（音调+光线），这种刺激复合体之前与它们的食物或药物摄入有关，这提供了一种线索诱导的渴望模型。我们已经证明（Nature, 412:141-2, 2001），对先前与可卡因摄入相关的刺激的反应在强制戒断自我给药的过程中增加（在强制戒断60天后增加13倍）。我们将这种现象称为“渴望的潜伏期”，并观察了大鼠自我服用蔗糖后的效果。在最近的研究中，我们发现大脑中与动机行为有关的区域伏隔核的失活，会减弱对可卡因或蔗糖的渴望的潜伏期。本实验将进一步探讨伏隔核在蔗糖经验动物贪爱效应孵化中的作用。多巴胺和谷氨酸在伏隔核中相互作用，并与复发行为有关。核心区和壳区在这方面也有区别。具体来说，我们建议在强迫戒断的第1天或第30天用多巴胺和谷氨酸受体拮抗剂挑战伏隔核和壳亚区，以阻止渴望的潜伏期。本提案中的所有实验都旨在允许本科生和硕士生充分参与通常为博士生和博士后研究人员保留的研究领域。这些实验将进一步加深我们对渴望效应孵化的理解，并将影响我们实验室未来拨款申请的方向。本项目所获得的信息也可能为药物成瘾和饮食失调的行为治疗和药物治疗提供指导。复发是药物和食物成瘾的特征。这些都是重大的公共卫生问题。本研究旨在确定复发的神经基质。

DESCRIPTION (provided by applicant): High rates of relapse characterize drug and food addiction. Relapse is often preceded by subjective reports of intense craving and these cravings can be induced by drug or food-paired stimuli. Rats will press a lever for the presentation of a stimulus complex (a tone + light) previously associated with their food or drug taking, providing a model of cue-induced craving. We have demonstrated (Nature, 412:141-2, 2001) that responding for a stimulus previously associated with cocaine intake increases over the course of forced abstinence from self-administration (13-fold increase by 60 days of forced abstinence). We labeled the phenomenon an "incubation of craving" and have observed the effect in rats following sucrose self- administration. In recent studies, we have found that inactivation of the nucleus accumbens, a brain region involved in motivated behavior, attenuates the incubation of craving for either cocaine or sucrose. The experiments outlined in this proposal will further explore the role of the nucleus accumbens in the incubation of craving effect in sucrose-experienced animals. Dopamine and glutamate are known to functionally interact in the nucleus accumbens and have been linked to relapse behaviors. Core and shell subregion distinctions have also been made in this regard. Specifically, we propose to attempt to block the incubation of craving by challenging accumbal core and shell subregions with antagonists of dopamine and glutamate receptors at Day 1 or Day 30 of forced abstinence. All experiments in this proposal are designed to allow full participation of undergraduate and master's level students in an area of research usually reserved for Ph.D. students and post-doctoral researchers. These experiments will further our understanding of the incubation of craving effect and will influence the direction of future grant proposals from our laboratory. Information gained from this project may also provide direction for behavioral therapy and medications-based therapy for drug addiction and eating disorders. Relapse characterizes drug and food addictions. These are major public health problems. The studies in this proposal aim to identify neural substrates of relapse.