Imaging the Neurobiology of a Behavioral Treatment

行为治疗的神经生物学成像

• 批准号: 7126896
• 负责人: Diana M Martinez
• 金额: $ 35.22万
• 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/7126896
• 关键词: behavior modification; behavior test; behavioral /social science research tag; bioimaging /biomedical imaging; carbon; clinical research; cocaine; dopamine; dopamine receptor; drug addiction; human subject; human therapy evaluation; methylphenidate; neurochemistry; neuroimaging; neurotransmitter transport; positron emission tomography; raclopride; radiotracer; reinforcer

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（由申请人提供）：在药物挑战之前和之后，用PET和[11C] RACLOPRIDE进行成像提供了可靠且非侵入性的衡量人脑内源性多巴胺的变化。先前的研究表明，可卡因依赖性与响应心理刺激挑战的多巴胺释放降低有关。我们最近完成了一项研究，该研究表明，这种突触前多巴胺功能的丧失与在存在替代增强剂的情况下自我管理可卡因的选择有关。重要的是，这一发现与增强动物模型一致，这表明多巴胺传播可调节基于奖励的行为，在这种情况下，可以在存在竞争增强器的情况下做出更适应性的反应。 先前的研究是在非治疗中使用住院实验室模型来衡量可卡因选择的非治疗寻求可卡因受试者的。因此，本提案的目的是在更现实的环境中调查这种关联，可卡因依赖于患者在使用可卡因和在治疗环境中呈现给他们的替代增强剂之间的选择。用代金券激励措施的社区加强方法是可卡因依赖性的一种治疗方法，在许多对照研究中都表现出了成功。由于这种疗法的基础是通过增加替代性，健康增强剂的密度来降低可卡因的增强价值，因此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。我们建议扫描40例可卡因依赖性[11C] raclopride和口服哌醋甲酯的患者，以测量多巴胺释放。将在治疗前和治疗12周时扫描患者。我们预测，在治疗前扫描中多巴胺传播损失最大的患者将是那些未能对治疗做出反应的患者。此外，我们假设对治疗做出反应的患者将经历在治疗后扫描中测量的多巴胺功能的恢复。 迄今为止，尚未对神经化学进行成像研究来研究神经化学与对可卡因依赖性行为治疗的反应之间的关系。此外，尽管这种治疗有效，但很大一部分患者可能无法做出反应。因此，这项研究的目标是为与治疗失败相关的神经生物学提供更好的了解，并最终的目的是开发改善这种行为疗法成功的方法。