Treatment for psychological dependence on morphine: usefulness of inhibiting NMDA receptor and its associated protein kinase in the nucleus accumbens.
A growing body of evidence indicates that the mesolimbic dopaminergic (DAergic) pathway projecting from the ventral tegmental area (VTA) to the nucleus accumbens (N.Acc.) play a critical role in the initiation of psychological dependence on morphine. As well as DAergic system, the involvement of non-DAergic neurotransmitter and neuromodulator systems in rewarding effects induced by morphine has been recently documented. We previously demonstrated that the morphine-induced rewarding effect was dramatically suppressed by co-treatment with NMDA receptor antagonists, such as dizocilpine (MK-801), ketamine and ifenprodil. Therefore, we propose here that inhibiting the N-methyl-D-aspartate (NMDA) receptor and its associated protein kinase in the N.Acc. is useful for the treatment for psychological dependence on morphine. The following review provides a summary of recent our findings regarding the role of NMDA receptor and its associated protein kinase in the development of psychological dependence on morphine.
Narita
Minoru
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. narita@hoshi.ac.jp
Kato
Hideaki
H
Miyoshi
Kan
K
Aoki
Takeshi
T
Yajima
Yoshinori
Y
Suzuki
Tsutomu
T
D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007649:Ketamine; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009021:Morphine Dependence / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D009714:Nucleus Accumbens / Q000378:metabolism*; D010880:Piperidines; D011493:Protein Kinase C / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*
C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D018691:Excitatory Amino Acid Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D011493:Protein Kinase C; C010739:ifenprodil