L-tetrahydropalmatine attenuates ketamine reward effect via modulating the miR-27a-3p/MAP2K4 axis.
Frontiers in genetics January 1, 2026 Yan Du, Xing-Cui Gao, Qing Ma et al.
Levo-tetrahydropalmatine (l-THP), an alkaloid from Chinese medicinal plants, reduces the rewarding effect of ketamine in rats, as measured by conditioned place preference. The compound activates the BDNF/TrkB signaling pathway and reverses increased expression of miR-27a-3p in ketamine-exposed rats and PC12 cells. Inhibiting miR-27a-3p in PC12 cells increases MAP2K4 expression, suggesting MAP2K4 is a functional target of this microRNA. These findings indicate that l-THP attenuates ketamine reward through modulation of the BDNF/TrkB pathway and the miR-27a-3p/MAP2K4 axis, which may offer targets for intervention.