Using PET to Image the Neurochemistry of Addiction

描述(申请人提供)：以前的临床和临床前研究表明，多巴胺传递的失调在药物滥用中起着关键作用。在这项申请中提出的研究包括候选人的工作，表征了在成瘾中看到的多巴胺传递的变化。这些研究包括在可卡因、酒精和海洛因依赖方面所做的研究，并表明这些障碍中的每一种都与D2/3受体结合和突触前多巴胺传递的丧失有关。重要的是，在可卡因依赖方面所做的工作表明，多巴胺的传递可以预测复发。下一步，除了研究直接调节多巴胺传递的其他神经递质系统外，还将探索导致多巴胺失调的机制。除了kappa和神经降压素受体系统外，这些研究还包括成像微核激活。候选人通过K23奖励机制发展了她的PET成像事业。由于该奖项提供的支持，她能够在物质依赖人群中从事成像研究。作为一名独立研究员，这位候选人一直在继续这项工作。此外，候选人在努力将PET放射配基成像引入更多类型的临床研究方面进行了大量的合作。K02奖项的申请将使候选人的职业生涯不受干扰地继续，因为她在PET成像领域寻求新的方向。 公共卫生相关性：该奖项的申请者之前进行的工作表明，多巴胺与药物成瘾有关。下一组研究将研究大脑多巴胺变化的原因以及纠正这种缺陷的方法。

DESCRIPTION (provided by applicant): Previous clinical and pre-clinical studies have shown that the dysregulation in dopamine transmission plays a critical role in substance abuse. The studies presented in this application include the candidate's work characterizing the alteration in dopamine transmission seen in addiction. These studies include research done in cocaine, alcohol, and heroin dependence, and show that each of these disorders is associated with a loss of D2/3 receptor binding and pre-synaptic dopamine transmission. Importantly, the work done in cocaine dependence shows that dopamine transmission is predictive of relapse. The next step is to explore the mechanisms that contribute to dopamine dysregulation in addition to studying other neurotransmitter systems that directly regulate dopamine transmission. These studies include imaging micriglial activation, in addition to the kappa and neurotensin receptors systems. The candidate developed her PET imaging career through the K23 award mechanism. Due to the support provided by that award, she was able to pursue a career in imaging studies in substance dependent populations. As an independent researcher, the candidate has continued this line of work. In addition, the candidate has pursued numerous collaborations in an effort to bring PET radioligand imaging into more types of clinical research. This application for a K02 award will allow the candidate's career to continue uninterrupted as she pursues new directions in PET imaging. PUBLIC HEALTH RELEVANCE: Previous work performed by the applicant for this award have shown that dopamine is involved in drug addiction. The next set of studies will examine the cause of the changes in brain dopamine and ways to correct this deficit.