The Role of the NR2B Subunit of NMDA Receptors in Morphine Rewarding, Drug Seeking, and Behavioral Sensitization

Abstract

Background: Studies indicate that the NR2B subunits of N-methyl-D-aspartate (NMDA) receptors are involved in the rewarding effects of morphine. In the present study we further investigated the role and action sites of the NR2B subunit of NMDA receptors in morphine rewarding and other behaviors related to drug addiction, such as drug seeking and behavioral sensitization. Methods: A selective antagonist of the NR2B subunit of NMDA receptors, ifenprodil, was locally injected into the nucleus accumbens (NAc) or ventral tegmental area (VTA) in male Sprague Dawley (S.D.) rats to block the NMDA receptors that contain NR2B subunits. A conditioned place preference (CPP) test was used to examine the rewarding and drugseeking effects. Locomotor activity tests were used to determine the behavioral sensitization induced by chronic morphine treatment. Results: Morphine-induced rewarding and drug-seeking behavior were abolished when the NR2B subunits of NMDA receptors at NAc were blocked by ifenprodil that was either coadministered with morphine during CPP conditioning or posttreated during the morphine-withdrawal period. In contrast, morphine still induced rewarding, drug-seeking behavior, and behavioral sensitization when ifenprodil was injected at the VTA. On the other hand, only when ifenprodil was coadministered with morphine did it partially inhibit the behavioral sensitization induced by morphine. Conclusions: These data imply that at least the NR2B subunits of NMDA receptors in the NAc, but not VTA, are involved in morphine-induced rewarding and drug-seeking effects.