Molecular Neuropsychiatry Research Branch, NIDA Intramural Research Program, Baltimore, MD 21224, USA.
Int J Mol Sci. 2021 Jan 27;22(3):1249. doi: 10.3390/ijms22031249.
Substance use disorders (SUDs) are ubiquitous throughout the world. However, much remains to be done to develop pharmacotherapies that are very efficacious because the focus has been mostly on using dopaminergic agents or opioid agonists. Herein we discuss the potential of using potassium channel activators in SUD treatment because evidence has accumulated to support a role of these channels in the effects of rewarding drugs. Potassium channels regulate neuronal action potential via effects on threshold, burst firing, and firing frequency. They are located in brain regions identified as important for the behavioral responses to rewarding drugs. In addition, their expression profiles are influenced by administration of rewarding substances. Genetic studies have also implicated variants in genes that encode potassium channels. Importantly, administration of potassium agonists have been shown to reduce alcohol intake and to augment the behavioral effects of opioid drugs. Potassium channel expression is also increased in animals with reduced intake of methamphetamine. Together, these results support the idea of further investing in studies that focus on elucidating the role of potassium channels as targets for therapeutic interventions against SUDs.
物质使用障碍（SUDs）在全球范围内普遍存在。然而，要开发非常有效的药物治疗方法仍有许多工作要做，因为重点主要集中在使用多巴胺能药物或阿片类激动剂上。在此，我们讨论了在 SUD 治疗中使用钾通道激活剂的潜力，因为有证据表明这些通道在奖赏药物的作用中起作用。钾通道通过对阈值、爆发性放电和放电频率的影响来调节神经元动作电位。它们位于被确定为对奖赏药物的行为反应很重要的脑区。此外，它们的表达谱受奖赏物质的给药影响。遗传研究也表明，编码钾通道的基因中的变异与它们有关。重要的是，钾激动剂的给药已被证明可以减少酒精摄入，并增强阿片类药物的行为效应。在摄入减少的安非他命的动物中，钾通道的表达也增加了。这些结果共同支持进一步投资于研究的想法，这些研究的重点是阐明钾通道作为治疗干预物质使用障碍的靶点的作用。
