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.
Keywords: Methamphetamine; Paeoniflorin; Rewarding effect; Synaptic protein; VTA.
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