Center for Physiology and Pharmacology, Medical University of Vienna, 1090, Vienna, Austria.
Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Neuropsychopharmacology. 2018 Nov;43(12):2408-2417. doi: 10.1038/s41386-018-0053-5. Epub 2018 Apr 6.
Amphetamine abuse is a major public health concern for which there is currently no effective treatment. To develop effective treatments, the mechanisms by which amphetamine produces its abuse-related effects need to be fully understood. It is well known that amphetamine exerts its actions by targeting high-affinity transporters for monoamines, in particular the cocaine-sensitive dopamine transporter. Organic cation transporter 3 (OCT3) has recently been found to play an important role in regulating monoamine signaling. However, whether OCT3 contributes to the actions of amphetamine is unclear. We found that OCT3 is expressed in dopamine neurons. Then, applying a combination of in vivo, ex vivo, and in vitro approaches, we revealed that a substantial component of amphetamine's actions is OCT3-dependent and cocaine insensitive. Our findings support OCT3 as a new player in the actions of amphetamine and encourage investigation of this transporter as a potential new target for the treatment of psychostimulant abuse.
苯丙胺滥用是一个主要的公共卫生关注点，但目前尚无有效的治疗方法。为了开发有效的治疗方法，需要充分了解苯丙胺产生其与滥用相关的作用的机制。众所周知，苯丙胺通过靶向单胺类物质的高亲和力转运体起作用，特别是可卡因敏感的多巴胺转运体。最近发现有机阳离子转运体 3（OCT3）在调节单胺信号中发挥重要作用。然而，OCT3 是否有助于苯丙胺的作用尚不清楚。我们发现 OCT3 表达于多巴胺神经元中。然后，通过应用体内、体外和体外的综合方法，我们揭示了相当一部分的苯丙胺作用是 OCT3 依赖性的，并且对可卡因不敏感。我们的研究结果支持 OCT3 作为苯丙胺作用的新参与者，并鼓励将该转运体作为治疗精神兴奋剂滥用的潜在新靶标进行研究。
