Spermidine, a positive modulator of the NMDA receptor, facilitates extinction and prevents the reinstatement of morphine-induced conditioned place preference in mice.

These results suggest that SPD facilitated the extinction of morphine-induced CPP by modulating the polyamine binding site of the NMDA receptor. Our findings reveal important effects of SPD and ifenprodil on the re-exposure-induced decrease in morphine-induced CPP, which may be promising for developing novel pharmacological strategies to treat opioid use disorder.