INCUBATION OF CRAVING: NEURAL SUBSTRATES

描述（由申请人提供）：药物成瘾治疗的限制因素是尽管昂贵的治疗干预措施，成瘾者的复发率很高。在开始戒断很久之后对毒品的渴望被认为是导致这种再犯的主要原因。在复发之前，通常会有对药物强烈渴望的主观报告。这种渴望可以通过先前与吸毒经历相关的刺激在个体中引起。线索诱导的渴望是在老鼠的实验过程中模拟的，在实验中，老鼠会按下一个杠杆，以呈现一个先前与他们服用药物相关的刺激复合物（音调+光线）。我们最近证明（Nature, 412:141-2, 2001.），对先前与可卡因自我注射相关的刺激的反应在戒断过程中逐渐增加（在戒断后第60天增加13倍）。我们把这种现象称为“渴望的孕育”。我们最近还观察到，对先前与口服自我给药蔗糖有关的刺激作出反应的大鼠的渴望效应潜伏期。本提案中概述的实验将探索在可卡因和蔗糖经验的动物中产生渴望效应的神经解剖学基础。基底外侧杏仁核和伏隔核将在这方面进行检查，在不同的退出时间点进行测试之前，使用每个结构的可逆失活程序。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。这些实验为渴望效应的孵化提供了初步的检验，并将影响我实验室未来RO1提案的方向。从这个项目中获得的信息将为行为治疗和基于药物的治疗渴望和复发提供指导。

DESCRIPTION (provided by applicant): The limiting factor in the treatment of drug addiction is the high rate of relapse seen in addicts, despite costly treatment interventions. Craving for the drug long after the initiation of abstinence is argued to be a primary contributor to this recidivism. Relapse is often preceded by subjective reports of intense craving for the drug. Such craving can be induced in an individual by the presentation of stimuli previously associated with their drug taking experiences. Cue-induced craving is modeled in procedures using rats wherein rats will press a lever for the presentation of a stimulus complex (a tone + light) previously associated with their drug taking. We have recently demonstrated (Nature, 412:141-2, 2001.) that responding for a stimulus previously associated with cocaine self-injections increases progressively over the course of withdrawal from self-administration (13-fold increase by day 60 of withdrawal). We have labeled the phenomenon an "incubation of craving". We have also recently observed the incubation of craving effect in rats responding for a stimulus previously associated with orally self-administered sucrose. The experiments outlined in this proposal will explore the neuroanatomical substrates of the incubation of craving effect in both cocaine- and sucrose-experienced animals. The basolateral amygdala and the nucleus accumbens will be examined in this regard using a procedure of reversible inactivation of each structure prior to testing at the different withdrawal time points. 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 provide an initial examination of the incubation of craving effect and will influence the direction of a future RO1 proposal from my laboratory. Information gained from this project will provide direction for behavioral therapy and medications-based therapy for craving and relapse.