Ide Soichiro, Iwase Noriaki, Arai Kenichi, Kojima Masahiro, Ushiyama Shigeru, Ikeda Kazutaka
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
UBE Corporation, Tokyo, Japan.
Neuropsychopharmacol Rep. 2025 Mar;45(1):e12503. doi: 10.1002/npr2.12503. Epub 2024 Nov 27.
Although methamphetamine (METH) and other addictive substance use disorders are a major social problem worldwide, appropriate pharmacotherapies have not yet been discovered. Subtype-nonselective opioid receptor antagonists, such as naltrexone (NTX), have been reported to suppress METH addiction, but unclear are the opioid receptor subtypes that are involved in this beneficial effect. To clarify the role of μ-opioid receptors (MOPs), we examined effects of the novel nonpeptidic MOP-selective antagonist UD-030 on the acquisition and expression of METH-induced conditioned place preference (CPP) using behavioral tests in C57BL/6J mice. UD-030 was found to inhibit both the acquisition and expression of METH-induced CPP in a dose-dependent manner, with effects comparable to those observed with NTX. These findings suggest that UD-030 has the potential to mitigate METH-related reward mechanisms and may serve as a promising candidate for MOP-selective pharmacotherapy targeting METH addiction.
尽管甲基苯丙胺（METH）和其他成瘾性物质使用障碍是全球范围内的一个主要社会问题，但尚未发现合适的药物疗法。据报道，亚型非选择性阿片受体拮抗剂，如纳曲酮（NTX），可抑制METH成瘾，但尚不清楚参与这种有益作用的阿片受体亚型。为了阐明μ-阿片受体（MOPs）的作用，我们使用行为测试，在C57BL/6J小鼠中研究了新型非肽类MOP选择性拮抗剂UD-030对METH诱导的条件性位置偏爱（CPP）的获得和表达的影响。发现UD-030以剂量依赖性方式抑制METH诱导的CPP的获得和表达，其效果与NTX相当。这些发现表明，UD-030有减轻与METH相关的奖赏机制的潜力，可能成为针对METH成瘾的MOP选择性药物治疗的有前景的候选药物。
