Inhibitory effects of the selective μ-opioid receptor antagonist UD-030 on methamphetamine-induced conditioned place preference.

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.