INCUBATION OF CRAVING: NEURAL SUBSTRATES

描述(由申请人提供)：吸毒成瘾治疗的限制因素是吸毒者的高复发率，尽管治疗干预费用高昂。在禁欲开始后很长时间内对毒品的渴望被认为是导致这种累犯的主要原因。在复发之前，往往会有对药物强烈渴望的主观报告。这种渴望可以通过呈现先前与吸毒经历有关的刺激而在个体中诱导。线索诱导的渴求是用大鼠的程序模拟的，在这些程序中，大鼠将按下杠杆，以呈现先前与其吸毒相关的刺激复合体(音调+光)。我们最近展示了(《自然》，412：141-2,2001)。在戒断自我给药的过程中，对以前与注射可卡因有关的刺激的反应逐渐增加(到戒断第60天增加了13倍)。我们将这一现象称为“渴望的孵化”。我们最近还观察到，在对先前口服蔗糖相关的刺激做出反应的大鼠中，渴望效应的孵化。这项提案中概述的实验将探索在经历可卡因和蔗糖的动物中孵化渴望效应的神经解剖学基础。在不同的退出时间点测试之前，将使用可逆失活每个结构的程序来检查杏仁基底外侧核和伏隔核。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。这些实验提供了对渴望效应孵化的初步检验，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疗法和基于药物的渴望和复发治疗提供方向。

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.