Psilocin suppresses methamphetamine‐induced hyperlocomotion and acquisition of conditioned place preference via D2R‐mediated ERK signaling
CNS Neuroscience & Therapeutics January 10, 2023 Jing Wang, Min Liang, Qing Shang et al. 23 citations
Psilocin, the active metabolite of psilocybin, counteracts methamphetamine (METH)-induced hyperactivity and blocks the formation of conditioned place preference (CPP) in mice, indicating it may reduce the rewarding effects of METH. In an acute model, 1 mg/kg psilocin reduced the elevated activity caused by 2 mg/kg METH. In the CPP model, the same dose of psilocin prevented the development of place preference during acquisition but did not affect extinction or relapse. Molecular analysis revealed that psilocin's effects involve altered expression of dopamine 2 receptor (D2R) and phosphorylated ERK in the prefrontal cortex, nucleus accumbens, and ventral tegmental area. Inhibitors of D2R and ERK phosphorylation also blocked METH-induced hyperactivity and CPP acquisition, suggesting psilocin acts through D2R-mediated regulation of ERK phosphorylation.