Brain research bulletin
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Brain research bulletin · Oct 2012
Essential role of NR2B-containing NMDA receptor-ERK pathway in nucleus accumbens shell in morphine-associated contextual memory.
Learned associations between the rewarding effect of addictive drugs and drug-paired contexts resist extinction and contribute to the high rate of relapse observed in drug addicts. Although it has been shown that extracellular signal-regulated kinase 1/2 (ERK1/2) activity in the nucleus accumbens (NAc) is modulated by the primary rewarding effect of opiates, little is known as to its role in the morphine-associated contextual memory. In the present study, we investigated the ERK1/2 activity indicated by phosphorylated ERK1/2 (pERK1/2) levels in rats using a morphine-induced conditioned place preference (CPP) procedure. ⋯ Bilateral injection of an inhibitor of ERK activation into the NAc shell attenuated ERK1/2 phosphorylation and prevented the expression of morphine CPP, but injections into the core did not. Selective inhibition of NR2B-containing NMDA receptor in the NAc shell by ifenprodil prevented CPP expression and down-regulated local ERK1/2 phosphorylation. These findings collectively suggest that recall of morphine-associated contextual memory depends specifically upon ERK1/2 activation in the NAc shell and that ERK1/2 phosphorylation is regulated by the upstream NR2B-containing NMDA receptor.