Effects of NMDA receptor antagonists (MK-801 and memantine) on the acquisition of morphine-induced conditioned place preference in mice.

Several studies have shown that the systemic administration of a variety of N-methyl-D-aspartate (NMDA) receptor antagonists can block the development or expression of conditioned place preference (CPP) induced by rewarding drugs such as morphine. In the present study, we examined the effects of different doses of two non-competitive NMDA receptor antagonists, MK-801 (0.1, 0.2 and 0.3 mg/kg) and memantine (2.5, 5, 10, 20 and 40 mg/kg), in CPP induced by 40 mg/kg of morphine in male mice. The CPP was carried out with an unbiased procedure in terms of initial spontaneous preference. Animals received the different doses of drugs in the conditioning sessions. MK-801 and memantine, at all doses used, produced neither place preference nor place aversion, but the higher doses of memantine (20 and 40 mg/kg) were able to completely block morphine-induced CPP. The present data show that the NMDA receptor antagonists MK-801 and memantine have no reinforcing properties but memantine is capable of preventing the acquisition of morphine-induced CPP. These results suggest that the development of morphine-induced CPP may be closely related to NMDA receptors and that the glutamatergic system can modulate opiate reward.