The effect of paeoniflorin on the rewarding effect of methamphetamine and the associated cognitive impairment in mice.

Chronic exposure to methamphetamine (METH) has been suggested to cause METH use disorder and severe cognitive impairment. Paeoniflorin (PF) is a monoterpenoid glycoside with various beneficial effects, including anti-inflammatory, antioxidant and antidepressant. The current study was designed to investigate the effect of PF (30 mg/kg, i.p.) on the rewarding effect of METH (2.5 mg/kg, i.p.) and the associated cognitive impairment, using the animal model of conditioned place preference, new location reorganization test, new object reorganization test and Y-maze test. METH induced conditioned place preference, accompanied by increased expression of synapse-associated proteins in the ventral target areas (VTA) and nucleus accumbens (NAc). In addition, METH induced significant cognitive impairment and decreased the expression of synapse-associated proteins in the hippocampus (Hip). Administration of PF decreased the rewarding effect of METH and the expression of synapse-associated proteins in the VTA or NAc. PF was also effective to improve METH-induced cognitive impairment by upregulating the expression of synapse-associated proteins in the Hip. Therefore, PF could be a potential agent for the treatment of METH use disorder and the associated cognitive impairment.