Incubation of Craving: Neural Substrates (competitive renewal)

渴望的孵化：神经基质（竞争性更新）

• 批准号: 7192336
• 负责人: JEFFREY W GRIMM
• 金额: $ 21.52万
• 依托单位: WESTERN WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7192336
• 关键词: Abstinence; Address; Animals; Applications Grants; Area; Attenuated; Behavior; Behavior Therapy; Brain region; Cocaine; Cognitive Therapy; Complex; Cues; Data; Doctor of Philosophy; Dopamine; Dopamine Antagonists; Dopamine Receptor; Eating Disorders; Food; Future; Glutamate Receptor; Glutamates; Intake; Label; Laboratories; Light; Link; Modeling; Nature; Nucleus Accumbens; Pharmaceutical Preparations; Postdoctoral Fellow; Public Health; Purpose; Rate; Rattus; Relapse; Reporting; Research; Research Personnel; Rewards; Role; Self Administration; Self-Administered; Stimulus; Students; Sucrose; Training; attenuation; base; craving; day; design; drug addiction therapy; experience; food addiction; motivated behavior; paired stimuli; relating to nervous system; research study

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.

描述（由申请人提供）：药物和食物成瘾的特点是复发率高。复发之前通常会出现强烈渴望的主观报告，这些渴望可能是由药物或食物搭配刺激引起的。老鼠会按下杠杆来呈现先前与它们的食物或药物摄入相关的刺激复合体（音调+光），从而提供提示诱导渴望的模型。我们已经证明（Nature，412：141-2，2001），在强制戒断自我给药的过程中，对先前与可卡因摄入相关的刺激的反应会增加（强制戒断 60 天增加 13 倍）。我们将这种现象称为“渴望的孵化”，并观察了大鼠自我施用蔗糖后的效果。在最近的研究中，我们发现伏隔核（涉及动机行为的大脑区域）的失活会减弱对可卡因或蔗糖的渴望的酝酿。该提案中概述的实验将进一步探索伏隔核在经历过蔗糖的动物的渴望效应孵化中的作用。已知多巴胺和谷氨酸在伏隔核中发生功能性相互作用，并与复发行为有关。在这方面还对核心次区域和外壳次区域进行了区分。具体来说，我们建议在强制戒断的第 1 天或第 30 天，通过用多巴胺和谷氨酸受体拮抗剂挑战伏核和壳亚区域来尝试阻止渴望的孵化。本提案中的所有实验旨在让本科生和硕士生充分参与通常为博士保留的研究领域。学生和博士后研究人员。这些实验将进一步加深我们对渴望效应的孕育的理解，并将影响我们实验室未来资助提案的方向。从该项目获得的信息还可以为药物成瘾和饮食失调的行为疗法和药物疗法提供指导。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。该提案中的研究旨在确定复发的神经基础。