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。在复发之前，通常会有强烈的渴望的主观报告，这些渴望可以由药物或与食物配对的刺激引起。大鼠将按下一个杠杆，以呈现先前与其食物或药物摄入相关的刺激复合体(音调+光)，提供线索诱导的渴望的模型。我们已经证明(自然，412：141-2,2001)，在强制戒除自我管理的过程中，对以前与可卡因摄入相关的刺激的反应会增加(强制戒除60天会增加13倍)。我们将这一现象称为“渴望的孵化”，并观察了蔗糖自身给药后对大鼠的影响。在最近的研究中，我们发现伏隔核失活，这是大脑中参与动机行为的区域，可以减弱对可卡因或蔗糖的渴望。这项提案中概述的实验将进一步探索伏隔核在蔗糖体验动物的渴求效应孵化中的作用。已知多巴胺和谷氨酸在伏隔核中功能上相互作用，并与复发行为有关。在这方面也对核心次区域和壳次区域进行了区分。具体地说，我们建议尝试在强制戒断的第1天或第30天用多巴胺和谷氨酸受体的拮抗剂挑战伏隔核心区和壳亚区，以阻止欲望的孵化。该提案中的所有实验都旨在允许本科生和硕士研究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提案的方向。从这个项目中获得的信息也可能为行为疗法和药物治疗药物成瘾和进食障碍提供方向。复发是毒品和食物成瘾的特征。这些都是主要的公共卫生问题。这项建议中的研究旨在确定复发的神经底物。

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.