Role of tyrosine kinase-dependent phosphorylation of NR2B subunit-containing NMDA receptor in morphine reward.

We previously demonstrated that the morphine-induced rewarding effect was dramatically suppressed by cotreatment with an NR2B subunit-containing N-methyl-D-aspartate (NMDA) receptor antagonist ifenprodil. Therefore we propose here that the NR2B subunit-containing NMDA receptor may be involved in the rewarding effect of morphine. A growing body of evidence indicates that tyrosine kinases, such as Src family kinases, increase the phosphorylation of the intracellular C-terminal tyrosine residues on the NR2B subunit and potentiate NMDA receptor function. The following review provides our recent findings regarding the role of tyrosine kinase-dependent phosphorylation of the NR2B subunit-containing NMDA receptor in the development of psychological dependence on morphine.