A new addiction model: Relapse triggered by cognitive stress

一种新的成瘾模型：认知压力引发的复发

• 批准号: 8383413
• 负责人: Courtney A Miller
• 金额: $ 9.9万
• 依托单位: SCRIPPS FLORIDA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8383413
• 关键词: AODD relapse; Acute; Address; Adult; Alcohols; Animal Model; Anxiety; Basic Science; Behavior; Behavior Control; Behavioral; Brain region; Child Abuse; Clinical Treatment; Cognitive; Cognitive Therapy; Cues; Drug usage; Emotional; Evaluation; Exposure to; Human; Individual; Intake; Laboratories; Life; Life Stress; Measures; Memory; Methamphetamine dependence; Methods; Mission; Modeling; National Institute of Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Neonatal; Neurons; Outcome; Patient Self-Report; Pharmaceutical Preparations; Physiological; Protocols documentation; Psychological Stress; Recruitment Activity; Rehabilitation therapy; Relapse; Reporting; Research; Research Personnel; Rewards; Risk; Rodent; Self Efficacy; Shock; Staining method; Stains; Stress; Substance Addiction; Substance abuse problem; Therapeutic; Work; abuse neglect; addiction; base; cellular imaging; clinically relevant; cognitive rehabilitation; coping; craving; disorder later incidence prevention; drug craving; drug of abuse; drug seeking behavior; effective therapy; experience; fighting; foot; improved; innovation; mature animal; new therapeutic target; novel; physiologic stressor; programs; psychologic; psychological stressor; psychostimulant; research clinical testing; stressor; substance abuse treatment; substance abuser; success; tool

DESCRIPTION (provided by applicant): Currently, clinicians can offer little hope to people addicted to psychostimulants - as many as 9 out of 10 will relapse within the first year of completing a rehabilitation program. Human studies of addiction model real world experience by inducing relapse with psychological stressors. Unfortunately, effective methods for inducing psychological stress in rodents are lacking at present, with most studies relying on physiological stressors. This need is addressed here with a Cognitive Stress (CoSt)-induced reinstatement model that uses non- invasive methods to induce cognitive stress (e.g. no need for physiologic stressors such as foot shock). The central hypothesis is that psychological stress will model the cognitive stress experienced by substance abusers after rehabilitation and reinstate drug seeking behavior in adult animals. In addition to being a means to elicit cognitive stress in adulthood, our use of early life stress reminders as one of the stressors has direct connections to addiction. Self-reports of childhood abuse and neglect are extremely high in addicts, up to 80- 90%. Consistent with this, animal models of early life stress reveal an increased vulnerability to drugs of abuse in adulthood. This project will determine the cognitive stressors that most effectively reinstate drug seeking behavior, as well as identify the brain regions that are activated by CoSt-induced reinstatement. The working hypothesis is that an acute psychological stressor or an olfactory reminder of early life stress will effectively reinstate drug seeking in ault rodents and recruit brain regions critical for emotional memory and reward- based strategies. The approach involves the simple union of common and widely used behavioral stressors (e.g. neonatal isolation) with reinstatement of drug seeking. In additional, through cellular imaging of activity in specific neuronal subtypes, the brain regions activated by CoSt-induced reinstatement will be identified. The contribution of the proposed research is simple, yet highly impactful - it s expected to yield the first animal model in which drug seeking behavior is reinstated by psychological stress. By mirroring the stress that substance abusers experience after rehabilitation, CoSt-induced reinstatement will provide a new platform with unprecedented clinical relevance for therapeutic discovery efforts. This model will be available to the entire fild, accelerating the missions of NIDA and NIAAA to treat substance and alcohol-related abuse and addiction. Further innovation of this approach lies in the integration and elevation of well-established behavior proto- cols to investigate relapse to drug seeking in an entirely new way; one that mirrors the post-rehabilitation struggle experienced by addicted individuals. Importantly, this approach has a high likelihood of success for the same reason - it involves the straightforward integration of well-established behavior protocols by a laboratory that has extensive experience with behavioral manipulations and addiction research. PUBLIC HEALTH RELEVANCE: By providing the first method to model relapse induced by psychological stress, the proposed project is anticipated to improve the clinical relevance of basic research efforts. This is expected to profoundly impact the field's ability to identify novel therapeutic targets for relapse prevention. Importantly, this invaluable tool will be available to ll researchers in the field, contributing significantly to the NIDA and NIAAA efforts towards developing effective treatments for substance abuse relapse.

描述（由申请人提供）：目前，临床医生对沉迷于心理刺激药的人几乎没有希望 - 在完成康复计划的第一年，多达10分的9分将复发。人类成瘾研究模型现实世界的经验，通过诱导心理压力源复发。不幸的是，目前缺乏诱导啮齿动物心理压力的有效方法，大多数研究依赖于生理压力源。此处以认知应力（成本）诱导的恢复模型来解决，该模型使用非侵入性方法诱导认知应力（例如，不需要诸如脚部冲击等生理压力源）。中心假设是，心理压力将模拟康复后滥用药物所经历的认知压力，并恢复成年动物的毒品寻求行为。除了成为成年后引起认知压力的一种手段外，我们将早期压力提醒的使用作为压力源之一，与成瘾有直接的联系。对童年虐待和忽视的自我报告在上瘾者中极高，高达80％至90％。与此一致，早期生活压力的动物模型表明，成年期间对滥用药物的脆弱性增加。该项目将确定最有效地恢复药物寻求行为的认知应激源，并确定由成本引起的恢复激活的大脑区域。工作的假设是，急性心理压力源或嗅觉提醒早期生活压力将有效地恢复在Ault Rodents中寻求药物，并招募对情绪记忆和基于奖励的策略至关重要的大脑区域。该方法涉及与恢复药物寻求的常见和广泛使用的行为应激源（例如新生儿隔离）的简单结合。另外，通过特定神经元亚型的活性的细胞成像，将确定由成本诱导的恢复激活的大脑区域。拟议的研究的贡献很简单，但影响力很大 - 预计将产生第一个动物模型，在这种动物模型中，心理压力恢复了吸毒行为。通过反映戒毒者在康复后经历的压力，成本引起的恢复将为一个新的平台提供前所未有的临床与治疗性发现工作相关性。该模型将适用于整个FILD，加速NIDA和NIAAA的任务，以治疗与酒精有关的滥用和成瘾。这种方法的进一步创新在于，良好行为的整合和提升原始的行为，以一种全新的方式研究对毒品的复发。一个反映了上瘾的人所经历的救助后斗争。重要的是， 这种方法具有很高的成功可能性，出于相同的原因 - 它涉及一项实验室与行为操纵和成瘾研究具有丰富经验的实验室完善的行为方案的直接整合。 公共卫生相关性：通过提供第一种由心理压力引起的复发的方法，预计拟议的项目将提高基础研究工作的临床相关性。预计这将严重影响该领域识别新颖的能力 预防复发的治疗靶标。重要的是，该无价的工具将为该领域的研究人员提供，这为NIAAA和NIAAA努力为开发有效的药物滥用复发疗法做出了重大贡献。