Imaging the Neurobiology of a Behavioral Treatment for Cocaine Dependence

可卡因依赖行为治疗的神经生物学成像

• 批准号: 7270656
• 负责人: Diana M Martinez
• 金额: $ 35.04万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270656
• 关键词: Abstinence; Address; Amphetamines; Animal Model; Animals; Asses; Behavior; Behavior Therapy; Brain; Characteristics; Chronic; Clinical Trials; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognitive Therapy; Communities; Controlled Study; Corpus striatum structure; Decision Making; Disease; Dopamine; Dopamine D2 Receptor; Dose; Drug Addiction; Drug usage; Enrollment; Ensure; Ethical Issues; Face; Failure; Future; Goals; Hospitalization; Human; Image; Impairment; Incentives; Inpatients; Invasive; Knowledge; Laboratories; Measures; Methods; Methylphenidate; Modeling; Motor; Neurobiology; Numbers; Oral; Outcome; Outpatients; Patients; Pharmaceutical Preparations; Play; Positron-Emission Tomography; Psychological reinforcement; Raclopride; Recovery; Refractory; Relapse; Research Personnel; Residential Treatment; Rewards; Role; Sampling; Scanning; Self Administration; Self-Administered; Synapses; Testing; Therapeutic; Treatment Efficacy; Treatment Failure; Treatment outcome; Week; base; comparison group; contingency management; density; design; experience; human study; improved; innovation; neurochemistry; pre-clinical; presynaptic; prognostic; programs; psychostimulant; radiotracer; receptor; reinforcer; response; success; therapy design; transmission process; treatment effect; trial comparing; volunteer; voucher

DESCRIPTION (provided by applicant): Imaging with PET and [11C] raclopride before and after a pharmacologic challenge provides a reliable and non-invasive measure of changes in endogenous dopamine in the human brain. Previous studies have shown that cocaine dependence is associated with a decrease in dopamine release in response to a psychostimulant challenge. We have recently completed a study demonstrating that this loss of pre-synaptic dopamine function is associated with the choice to self-administer cocaine in the presence of an alternative reinforcer. Importantly, this finding consistent with animal models of reinforcement and which show that dopamine transmission serves to modulate reward based behavior, and in this case, allow for a more adaptive response to be made in the presence of a competing reinforcer. The previous study was performed in non-treatment seeking cocaine dependent subjects using an inpatient laboratory model to measure the choice for cocaine. Thus, the goal of the present proposal is to investigate this association in a more realistic setting where cocaine dependent out patients face the choice between using cocaine and the alternative reinforcers presented to them in a therapeutic setting. The Community Reinforcement Approach with voucher incentives is a treatment for cocaine dependence that has been shown success in a number of controlled studies. Since the basis of this therapy is to reduce the reinforcing value of cocaine by increasing the density of alternative, healthy reinforcers, we have chosen to correlate outcome from this treatment with measures of presynaptic dopamine function. We propose to scan 40 cocaine dependent patients with [11C] raclopride and oral methylphenidate in order to measure dopamine release. Patients will be scanned before treatment and at 12 weeks into therapy. We predict that the patients with the greatest loss of dopamine transmission at the pre-treatment scan will be those who fail to respond to treatment. Furthermore, we hypothesize that the patients who do respond to treatment will experience a recovery of dopamine function, measured at the post-treatment scan. To date, no imaging studies of neurochemistry have been performed to investigate the relationship between neurochemistry and response to a behavioral treatment for cocaine dependence. Furthermore, despite the efficacy of this treatment, a substantial proportion of patients are likely to fail to respond. Thus the objectives of this study are to provide a better understanding of the neurobiology associated with treatment failure, with an ultimate goal of developing methods to improve the success of this behavioral therapy.

描述(申请人提供)：PET和[11C]拉氯必利在药物挑战前后的成像提供了一种可靠的、非侵入性的人类大脑内源性多巴胺变化的测量方法。以前的研究表明，可卡因依赖与应对精神刺激挑战的多巴胺释放减少有关。我们最近完成了一项研究，证明这种突触前多巴胺功能的丧失与选择在替代增强剂存在的情况下自我给药有关。重要的是，这一发现与强化的动物模型相一致，该模型表明，多巴胺传递用于调节基于奖励的行为，在这种情况下，允许在竞争的强化者存在的情况下做出更适应的反应。 先前的研究是在寻求可卡因依赖的非治疗受试者中进行的，使用住院实验室模型来衡量对可卡因的选择。因此，本提案的目标是在更现实的情况下调查这种联系，在这种情况下，可卡因依赖门诊患者面临在治疗环境中使用可卡因和提供给他们的替代增强剂之间的选择。使用代金券奖励的社区强化方法是一种治疗可卡因依赖的方法，在一些对照研究中证明是成功的。由于这种疗法的基础是通过增加替代的、健康的增强剂的密度来降低可卡因的强化价值，我们选择将这种治疗的结果与突触前多巴胺功能的测量相关联。我们建议用[11C]拉克洛必利和口服哌醋甲酯扫描40名可卡因依赖患者，以测量多巴胺的释放。患者将在治疗前和治疗后12周进行扫描。我们预测，在治疗前扫描中，多巴胺传递损失最大的患者将是那些对治疗无效的患者。此外，我们假设对治疗有反应的患者将经历多巴胺功能的恢复，这是在治疗后扫描时测量的。 到目前为止，还没有进行神经化学的成像研究来调查神经化学和对可卡因依赖的行为治疗反应之间的关系。此外，尽管这种治疗有效，但很大一部分患者可能没有反应。因此，这项研究的目的是为了更好地了解与治疗失败相关的神经生物学，最终目的是开发方法来提高这种行为治疗的成功。