FUNCTIONAL BRAIN ACTIVITY AFTER COCAINE USE & EXTINCTION THERAPY IN NHP

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目前，还没有FDA批准的治疗兴奋剂成瘾的药物。虽然可卡因对大脑功能的急性影响已经有了很好的特征，但对与长期药物使用有关的大脑功能的长期变化却知之甚少。防止复发往往是治疗药物成瘾最困难的障碍。在长期戒毒的患者中，暴露于与药物使用相关的环境线索会导致复发，这是众所周知的。最近有证据表明，消解训练在治疗其他精神疾病方面可能有显著效果。然而，这种方法并没有在药物成瘾的背景下得到有效的实施，而且几乎对与消退疗法相关的神经生物学一无所知。在恒河猴身上正在进行的研究正在评估在有限和长期获得可卡因自我给药、药物戒断和消退训练后大脑功能的变化。线索诱导的可卡因自我给药恢复提供了与滥用相关的行为结果，与神经生物学相关。具体地说，我们正在用BOLD fMRI记录可卡因暴露和消退训练对静息状态和线索诱导的脑功能活动的影响。禁欲和消亡状态之间的直接比较将验证消退疗法的有效性和神经生物学机制。该研究项目具有很高的创新性，其重点是灭绝训练和大脑功能活动，其范式模拟了可卡因使用到依赖和成瘾的过程。我们研究的长期目标是确定有效的可卡因药物疗法的目标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Currently, there are no FDA-approved medications to treat stimulant addiction. While the acute effects of cocaine on brain function have been well characterized, much less is known about the long-term changes in brain function associated with chronic drug use. Preventing relapse is often the most difficult obstacle in treating drug addiction. It is well recognized that exposure to environmental cues associated with drug use can induce relapse in patients who have been abstinence for extended periods. There is recent evidence that extinction training may have significant efficacy in the treatment of other psychiatric disorders. However, this approach has not been effectively implemented in the context of drug addiction and virtually nothing is known about the neurobiology associated with extinction therapy. Ongoing studies in rhesus monkeys are evaluating changes in brain function following limited- and extended-access to cocaine self-administration, drug abstinence, and extinction training. Cue-induced reinstatement of cocaine self-administration provides an abuse-related behavioral outcome to correlate with neurobiology. Specifically, we are documenting the effects of cocaine exposure and extinction training on resting state and cue-induced functional brain activity with BOLD fMRI. Direct comparisons between abstinence and extinction conditions will validate the usefulness and neurobiological mechanisms of extinction therapy. The research project is highly innovative in its focus on extinction training and functional brain activity in a paradigm that models the progression of cocaine use to dependence and addiction. The long-term goal of our research is to identify targets for effective cocaine pharmacotherapies.