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.

中文翻译：

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有机阳离子转运蛋白 3 在苯丙胺作用中的意外作用。

苯丙胺滥用是一个主要的公共卫生问题，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滥用相关影响的机制。众所周知，苯丙胺通过靶向单胺的高亲和力转运蛋白，特别是对可卡因敏感的多巴胺转运蛋白发挥作用。最近发现有机阳离子转运蛋白 3 (OCT3) 在调节单胺信号传导中起重要作用。然而，OCT3 是否有助于苯丙胺的作用尚不清楚。我们发现 OCT3 在多巴胺神经元中表达。然后，应用体内、体外和体外方法的组合，我们发现苯丙胺作用的重要组成部分是 OCT3 依赖性和可卡因不敏感的。