INCUBATION OF CRAVING: NEURAL SUBSTRATES

渴望的孕育：神经基质

• 批准号: 6952593
• 负责人: JEFFREY W GRIMM
• 金额: $ 4.98万
• 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 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6952593
• 关键词: amygdala; behavior test; behavioral /social science research tag; cocaine; craving; drug /alcohol abstinence; drug addiction; drug withdrawal; histochemistry /cytochemistry; laboratory rat; nucleus accumbens; relapse /recurrence; sucrose

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.

描述（由申请人提供）：药物成瘾治疗的限制因素是成瘾者的复吸率很高，尽管治疗干预费用很高。在开始禁欲后很久对药物的渴望被认为是这种累犯的主要原因。复发之前通常会有对药物强烈渴望的主观报告。这种渴望可以通过呈现先前与其吸毒经历相关的刺激而在个体中诱导。在使用大鼠的程序中对线索诱导的渴望进行建模，其中大鼠将按压杠杆以呈现先前与其药物服用相关的刺激复合物（音调+光）。我们最近已经证明了（自然，412：141-2，2001）。对先前与可卡因自我注射相关的刺激的响应在从自我施用戒断的过程中逐渐增加（到戒断的第60天增加13倍）。我们把这种现象称为“渴望的孵化”。我们最近还观察到大鼠对先前与口服自我给药蔗糖相关的刺激的渴求效应的孵化。在这个建议中概述的实验将探讨可卡因和蔗糖经验的动物的渴求效应的孵化的神经解剖学基板。在这方面，在不同的停药时间点进行试验之前，将使用每个结构的可逆失活程序检查基底外侧杏仁核和杏仁核。本提案中的所有实验都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。 这些实验提供了一个初步的研究渴望效应的孵化，并将影响未来的方向RO 1建议从我的实验室。从这个项目中获得的信息将提供方向的行为治疗和药物为基础的治疗渴望和复发。