Abstract: To investigate the effect of rhynchophylline on the expression of NMDA receptor 2B subunit (NR2B) in methamphetamine-induced condition place preference (CPP) in zebrafish.Zebrafish were randomly divided into control group,model group (methamphetamine 40 mg/kg),ketamine (150 mg/kg),rhynchophylline (40 mg/kg) group and rhynchophylline (80 mg/kg) group.After intraperitoneal injection of methamphetamine,zebrafish CPP training was carried out,and the methamphetamine CPP-dependent zebrafish model was established.The activity of zebrafish in CPP compartment and the expression of NR2B in zebrafish brain were analyzed.Compared with control group,the residence time of model group in drug pair compartment was significantly increased.Compared with model group,the residence time of rhynchophylline (80 mg/kg) group in drug pair compartment was significantly decreased.The result of immunohistochemistry showed that methamphetamine (40 mg/kg) increased the number of NR2B positive cells in zebrafish brain.However,treatment with ketamine (150 mg/kg),rhynchophylline (40,80 mg/kg) reduced the number of NR2B positive cells in zebrafish brain.Western blot indicated the expression of NR2B of model group increased significantly.The zebrafish in ketamine (150 mg/kg) and rhynchophylline (80 mg/kg) group had less NR2B expression.NR2B plays a key role in the methamphetamine-induced CPP in zebrafish.Rhynchophylline reverses methamphetamine-induced CPP by regulating the expression of NR2B in zebrafish.

Key words: rhynchophylline, methamphetamine, condition place preference, NR2B, zebrafish