QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 23, 2003, 23(16):6529-6536

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (42) Citing Articles via Google Scholar Google Scholar Articles by Inoue, M. Articles by Ueda, H. Search for Related Content PubMed PubMed Citation Articles by Inoue, M. Articles by Ueda, H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB MORPHINE NITRIC OXIDE

 Previous Article  |  Next Article 

Locus-Specific Rescue of GluR1 NMDA Receptors in Mutant Mice Identifies the Brain Regions Important for Morphine Tolerance and Dependence

Makoto Inoue,¹ Masayoshi Mishina,^2,3 and Hiroshi Ueda¹

¹Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8521, Japan, ²Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan, and ³Solution-Oriented Research for Science and Technology, Japan Science and Technology Corporation, Tokyo 113-0033, Japan

Tolerance and physical dependence caused by chronic treatment of narcotics are good models to study basic neuronal plasticity. Activation of the NMDA subtype of the glutamate receptor has been implicated as an anti-opioid system in the development of morphine analgesic tolerance and dependence. The present study examines the specific role of the 1 subunit of the NMDA receptor using mice lacking the gene encoding 1 subunit of the NMDA receptor (GluR1^-/- mice). GluR1^-/- mice showed significant enhancement and prolongation of morphine anti-nociception, compared with wild-type GluR1^+/+ mice. GluR1^-/- mice also showed a marked loss of the analgesic tolerance after repeated morphine treatments. In C57BL/6J mice treated with chronic morphine after tolerance paradigm, the GluR1 protein expression significantly increased in periaqueductal gray matter (PAG), ventral tegmental area (VTA) and nucleus accumbens (NAc), but not amygdala or hippocampus. The rescue of GluR1 protein by electroporation into the PAG and VTA, but not NAc of GluR1^-/- mice significantly reversed morphine analgesic tolerance liability. Similar attempts were also performed in the naloxone-precipitated physical dependence paradigm. GluR1^-/- mice showed marked loss of typical withdrawal abstinence behaviors, and significant enhancement of GluR1 protein expression was only observed in NAc by chronic morphine treatments after dependence paradigm. The rescue of GluR1 protein by electroporation into the NAc of GluR1^-/- mice significantly reversed the loss of abstinence behaviors. These findings suggest that GluR1 has locus-specific roles in the development of morphine analgesic tolerance and physical dependence.

Key words: NMDA receptor; 1 subunit; morphine tolerance and dependence; KO mice; locus-specific rescue; neuronal network

---

Received Feb. 24, 2003; revised May. 13, 2003; accepted May. 20, 2003.

This article has been cited by other articles:

				W.-T. Liu, H.-C. Li, X.-S. Song, Z.-J. Huang, and X.-J. Song EphB receptor signaling in mouse spinal cord contributes to physical dependence on morphine FASEB J, January 1, 2009; 23(1): 90 - 98. [Abstract] [Full Text] [PDF]

				G. Gu, I. Kondo, X.-Y. Hua, and T. L. Yaksh Resting and Evoked Spinal Substance P Release during Chronic Intrathecal Morphine Infusion: Parallels with Tolerance and Dependence J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1362 - 1369. [Abstract] [Full Text] [PDF]

				B. Bie, Y. Peng, Y. Zhang, and Z. Z. Pan cAMP-Mediated Mechanisms for Pain Sensitization during Opioid Withdrawal J. Neurosci., April 13, 2005; 25(15): 3824 - 3832. [Abstract] [Full Text] [PDF]

				N. Takayama and H. Ueda Morphine-Induced Chemotaxis and Brain-Derived Neurotrophic Factor Expression in Microglia J. Neurosci., January 12, 2005; 25(2): 430 - 435. [Abstract] [Full Text] [PDF]

				G. Martin, A. Guadano-Ferraz, B. Morte, S. Ahmed, G. F. Koob, L. de Lecea, and G. R. Siggins Chronic Morphine Treatment Alters N-Methyl-D-aspartate Receptors in Freshly Isolated Neurons from Nucleus Accumbens J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 265 - 273. [Abstract] [Full Text] [PDF]

				V. Zachariou, D. Georgescu, N. Sanchez, Z. Rahman, R. DiLeone, O. Berton, R. L. Neve, L. J. Sim-Selley, D. E. Selley, S. J. Gold, et al. Essential role for RGS9 in opiate action PNAS, November 11, 2003; 100(23): 13656 - 13661. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help