Using PET to Image the Neurochemistry of Addiction

描述（由申请人提供）：以往的临床和临床前研究表明，多巴胺传递失调在药物滥用中起关键作用。在本申请中提出的研究包括候选人的工作表征在成瘾中看到的多巴胺传递的改变。这些研究包括对可卡因、酒精和海洛因依赖的研究，并表明这些疾病中的每一种都与D2/3受体结合和突触前多巴胺传递的丧失有关。重要的是，对可卡因依赖的研究表明，多巴胺的传递预示着毒瘾的复发。除了研究直接调节多巴胺传递的其他神经递质系统外，下一步是探索导致多巴胺失调的机制。这些研究包括成像微神经激活，除了kappa和神经紧张素受体系统。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，她能够从事物质依赖人群的成像研究。作为一名独立研究人员，候选人继续从事这方面的工作。此外，该候选人在努力将PET放射配位成像带入更多类型的临床研究方面进行了多次合作。这个申请K02奖将允许候选人的职业生涯不间断地继续，因为她追求PET成像的新方向。

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.