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使用 PET 和[11C]雷氯必利进行成像提供了人脑内源性多巴胺变化的可靠且非侵入性的测量。先前的研究表明，可卡因依赖与精神兴奋剂挑战引起的多巴胺释放减少有关。我们最近完成的一项研究表明，这种突触前多巴胺功能的丧失与在存在替代强化剂的情况下选择自我施用可卡因有关。重要的是，这一发现与强化动物模型一致，并且表明多巴胺传递有助于调节基于奖励的行为，并且在这种情况下，允许在存在竞争性强化物的情况下做出更具适应性的反应。 之前的研究是在非寻求治疗的可卡因依赖受试者中进行的，使用住院实验室模型来衡量可卡因的选择。因此，本提案的目标是在更现实的环境中研究这种关联，在该环境中，可卡因依赖患者面临使用可卡因和在治疗环境中向他们提供的替代强化剂之间的选择。带有优惠券激励的社区强化方法是治疗可卡因依赖的一种方法，许多对照研究已证明该方法取得了成功。由于这种疗法的基础是通过增加替代的健康强化物的密度来降低可卡因的强化价值，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。我们建议使用 [11C] 雷氯必利和口服哌甲酯对 40 名可卡因依赖患者进行扫描，以测量多巴胺释放。患者将在治疗前和治疗后 12 周接受扫描。我们预测，在治疗前扫描中多巴胺传输损失最大的患者将是那些对治疗没有反应的患者。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（在治疗后扫描中测量）。 迄今为止，尚未进行神经化学成像研究来调查神经化学与可卡因依赖行为治疗反应之间的关系。此外，尽管这种治疗有效，但相当一部分患者可能无法做出反应。因此，本研究的目的是更好地理解与治疗失败相关的神经生物学，最终目标是开发提高这种行为疗法成功率的方法。