Implication of Src family kinase-dependent phosphorylation of NR2B subunit-containing NMDA receptor in the rewarding effect of morphine.
The present study was undertaken to further clarify the role of tyrosine phosphorylation of NR2B subunit-containing N-methyl-D-aspartate (NMDA) receptor in the development of the morphine-induced rewarding effect in mice. The morphine (5 mg/kg, sc)-induced rewarding effect was completely inhibited by pretreatment with a selective NR2B subunit-containing NMDA receptor antagonist ifenprodil (20 mg/kg, i.p.). The protein level of phospho-Tyr-1472, but not phospho-Ser-1303, NR2B subunit was significantly increased in the mouse limbic forebrain containing the nucleus accumbens (N.Acc.) of mice that had shown the morphine-induced rewarding effect. In addition, the level of phospho-Tyr-416 Src family kinase was also increased in the limbic forebrain of mice that had shown the morphine-induced rewarding effect. These findings suggest that Tyr-1472 phosphorylation of NR2B subunit-containing NMDA receptor associated with activation of Src family kinase in the limbic forebrain may be involved in the morphine-induced rewarding effect.
Kato
Hideaki
H
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Narita
Minoru
M
Miyoshi
Kan
K
Narita
Michiko
M
Asato
Megumi
M
Hareyama
Nana
N
Nozaki
Hiroyuki
H
Takagi
Tomoe
T
Suzuki
Masami
M
Suzuki
Tsutomu
T
D000818:Animals; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000378:metabolism; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012201:Reward; D019061:src-Family Kinases / Q000502:physiology*
C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine; D019061:src-Family Kinases; C010739:ifenprodil