Variation in the abilty of drug cues to reinstate drug seeking

药物线索恢复药物寻求能力的变化

• 批准号: 8353013
• 负责人: Benjamin Thomas Saunders
• 金额: $ 1.54万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8353013
• 关键词: Abstinence; Address; Animals; Attention; Behavior; Behavior Control; Cocaine; Conflict (Psychology); Corpus striatum structure; Cues; Development; Dopamine; Drug usage; Exposure to; Extinction (Psychology); Food; Future; Goals; Human; Incentives; Individual; Intervention; Location; Measures; Mediating; Modeling; Motivation; Neurobiology; Nucleus Accumbens; Pharmaceutical Preparations; Pre-Clinical Model; Predisposition; Procedures; Property; Public Health; Rattus; Relapse; Research; Rewards; Risk Factors; Role; Scanning; Series; Signal Transduction; Stimulus; Therapeutic Intervention; United States; Variant; Work; addiction; adverse outcome; base; classical conditioning; craving; drug craving; drug relapse; drug seeking behavior; experience; neurobiological mechanism; preclinical study; psychologic; reinforcer; research study; response; transmission process

DESCRIPTION (provided by applicant): Addicts have great difficulty resisting cues that have been associated with drug use. Such cues attract their attention, draw them to locations where drugs are located, and motivate continued drug-seeking behavior - often leading to relapse even in the face of an expressed desire to discontinue drug use. Drug cues are thought to acquire incentive motivational properties ("incentive salience") as a consequence of Pavlovian conditioning, whereby previously neutral stimuli acquire conditional stimulus (CS) properties. However, in preclinical studies using rats we have discovered that individuals vary markedly in the extent to which they attribute incentive salience to reward cues. A reward cue may act as a perfectly effective CS, evoking a conditional response (CR) in all animals, but function as a potent incentive stimulus only in some. Only if reward cues act as incentive stimuli do they come to attract, instigate, spur, and motivate, leading to potentially maladaptive behavior. I hypothesize, therefore, that individuals prone to attribute incentive salience to reward cues will have particular difficulty resisting them and will be especially vulnerable to relapse. Indeed, there is considerable variation in the ability of drug cues to instigate drug craving and relapse. Moreover, the degree that such cues increase the desire to take drug is correlated with how much the cue increases dopamine (DA) transmission. In the current application, I propose a series of preclinical studies to investigate individual variation in relapse behavior and its relationship with DA transmission (as measured using fast-scan cyclic voltammetry). This proposal will address the following questions: 1) Does individual variation in the tendency to attribute incentive value to reward cues predict variation in reinstatement to noncontingent drug cues? and 2) Do differences in phasic DA release encode variation in cue-induced reinstatement? These studies have the potential to significantly shift how we think about individual vulnerability to addiction and relapse, and point toward better-targeted interventions.

描述（由申请人提供）：吸毒者在抵抗与吸毒相关的线索方面有很大的困难。这样的提示吸引了他们的注意力，将它们吸引到毒品所在的地方，并激励继续寻求毒品的行为 - 即使面对表达停止使用毒品的渴望，也常常导致复发。人们认为药物提示会因帕夫洛维亚调节而获得激励动机（“激励显着性”），因此以前中性刺激获得了条件刺激（CS）。但是，在使用大鼠的临床前研究中，我们发现个体在将激励性的显着性奖励的程度上明显变化。奖励提示可以充当完全有效的CS，引起所有动物中有条件的反应（CR），但仅在某些动物中充当有效的激励刺激。只有当奖励提示作为激励刺激时，才能吸引，煽动，刺激和激励，从而导致潜在的适应不良行为。因此，我假设很容易将激励性的显着性归因于提示，这将在抵抗它们方面特别困难，并且特别容易发生复发。确实，药物提示激发药物渴望和复发的能力有很大差异。此外，这种提示增加吸毒的愿望的程度与提示增加了多巴胺（DA）的传播程度。在当前的应用中，我提出了一系列临床前研究，以研究复发行为中的个体变化及其与DA传播的关系（如使用快速扫描的循环伏安法测量）。该提案将解决以下问题：1）趋势的趋势是否将激励价值的趋势变异奖励提示预测恢复的变化变化为非敏化药物提示？ 2）在提示诱导的恢复中，阶段DA释放的编码变化是否存在差异？这些研究有可能显着转移我们对成瘾和复发的个人脆弱性的看法，并指向靶向更好的干预措施。