title: Essential role of NR2B-containing NMDA receptor-ERK pathway in nucleus accumbens shell in morphine-associated contextual memory.
abstract: 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. Our results showed that, in rats that had undergone morphine conditioning, after testing (expression phase) pERK1/2 in the NAc shell but not the NAc core or the adjacent caudate putamen was specifically increased. pERK1/2 levels in several other parts of the brain involved in drug-seeking, such as the medial prefrontal cortex, dorsal hippocampus, and basolateral amygdala, showed no significant changes. A significant positive correlation was observed between the elevated pERK1/2 level in the NAc shell and the degree of conditioned preference for morphine-associated contexts. 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.
authors: Neuroscience Research Institute, Peking University, Beijing, PR China.
authors: Ya
authors: Y
authors: Xu
authors: Xiu-Fang
authors: XF
authors: Lv
authors: Cai-Lian
authors: CL
authors: Cui
authors: Fei-Fei
authors: FF
authors: Ge
authors: Yi-Jing
authors: YJ
authors: Li
authors: Hao-Lin
authors: HL
authors: Zhang
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine