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 b...

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Published inNihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology Vol. 26; no. 3; p. 119
Main Authors Kato, Hideaki, Narita, Minoru, Miyoshi, Kan, Narita, Michiko, Asato, Megumi, Hareyama, Nana, Nozaki, Hiroyuki, Takagi, Tomoe, Suzuki, Masami, Suzuki, Tsutomu
Format Journal Article
LanguageEnglish
Published Japan 01.06.2006
Subjects
Animals
Male
Mice
Mice, Inbred ICR
Morphine - antagonists & inhibitors
Morphine - pharmacology
Nucleus Accumbens - metabolism
Phosphorylation
Piperidines - pharmacology
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - physiology
Reward
src-Family Kinases - physiology
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Summary: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.
ISSN:1340-2544