FUNCTIONAL BRAIN ACTIVITY AFTER COCAINE USE & EXTINCTION THERAPY IN NHP

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目前，没有FDA批准的药物来治疗兴奋剂成瘾。虽然可卡因对大脑功能的急性影响已经得到了很好的描述，但对与长期吸毒有关的大脑功能的长期变化却知之甚少。预防复吸往往是治疗吸毒成瘾最困难的障碍。众所周知，暴露于与药物使用相关的环境线索可诱导长期禁欲的患者复发。最近有证据表明，灭绝训练可能对其他精神疾病的治疗有显着疗效。然而，这种方法在药物成瘾的背景下并没有得到有效的实施，并且几乎对与灭绝疗法相关的神经生物学一无所知。正在进行的恒河猴研究正在评估有限和延长可卡因自我给药、药物戒断和灭绝训练后脑功能的变化。提示诱导可卡因自我给药的恢复提供了与神经生物学相关的滥用相关的行为结果。具体来说，我们正在记录可卡因暴露和灭绝训练对静息状态和线索诱导的功能性脑活动的影响与BOLD fMRI。禁欲和灭绝条件之间的直接比较将验证灭绝疗法的有效性和神经生物学机制。该研究项目在专注于灭绝训练和功能性大脑活动方面具有高度创新性，该模式模拟了可卡因使用到依赖和成瘾的进展。我们研究的长期目标是确定有效的可卡因药物治疗的目标。

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.