N-methyl-D-aspartic acid-receptor antagonists block morphine-induced conditioned place preference in rats.

We addressed the question of whether (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) and DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP37849), a non-competitive and a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, respectively, are able to block morphine-induced conditioned place preference (CPP). MK-801 alone (0.1 mg/kg) produced neither a place preference nor a place aversion, but was able to completely block morphine-induced CPP. CGP37849 alone (10 mg/kg) produced a small but significant CPP, and was able to significantly attenuate morphine-induced CPP. These results cannot be due to simple additive effects of drug actions, but suggest that NMDA receptors play a complex role in the development of morphine CPP.