NR2B subunit of NMDA receptor at nucleus accumbens is involved in morphine rewarding effect by siRNA study

Chronic use of morphine causes rewarding effects and behavioral sensitization, which may lead to the development of craving for morphine. A number of studies indicate that the NMDA receptors may be involved in these effects, especially the NR2B-containing NMDA receptors. It is also well recognized that the nucleus accumbens (NAc) and the ventral tegmental area (VTA) are involved in drug addiction, including morphine addiction.

In this study, we further investigate the role of the NR2B subunit of NMDA receptors at NAc or VTA in morphine rewarding effects and behavioral sensitization.

The siRNA against the NR2B subunit of NMDA receptors was locally injected to decrease the expression of NR2B at NAc or posterior VTA in male Sprague-Dawley (S.D.) rats in the present study. The rats were then treated with morphine chronically. A conditioned place preference (CPP) test was used to examine the rewarding effect, and locomotor activity was measured to determine the behavioral sensitization induced by chronic morphine treatment. Results showed that morphine-induced rewarding behavior but not behavioral sensitization was abolished when the NR2B subunit of NMDA receptors at the NAc were significantly decreased. The dopamine turnover rate was not altered by the decrease of NR2B subunit at NAc.

These findings suggest that the NR2B subunit of NMDA receptors at the NAc is involved in morphine-induced rewarding effect and may not be through directly interacting with dopamine neurons.