Opiate physical dependence and N-methyl-D-aspartate receptors

Yukihiro Noda, Toshitaka Nabeshima

Research output: Contribution to journalReview article

48 Citations (Scopus)

Abstract

The present review focused the involvement of N-methyl-d-aspartate (NMDA) receptors in morphine physical dependence. The increased levels of extracellular glutamate, NMDA receptor ζ subunit (NR1) mRNA, NMDA receptor ε1 subunit (NR2A) protein, phosphorylated Ca 2+/calmodulin kinase II (p-CaMKII) protein, c-fos mRNA, c-Fos protein, are observed in the specific brain areas of mice and/or rats showing signs of naloxone-precipitated withdrawal. In preclinical and clinical studies, a variety of NMDA receptor antagonists and pretreatment with an antisense oligonucleotide of the NR1 have been reported to inhibit the development, expression and/or maintenance of opiate physical dependence. In contrast to data obtained in adult animals, NMDA receptor antagonists are neither effective in blocking the development of opiate dependence nor the expression of opiate withdrawal in neonatal rats. In the NMDA receptor-deficient mice, the NR2A knockout mice show the marked loss of typical withdrawal abstinence behaviors precipitated by naloxone. The rescue of NR2A protein by electroporation into the nucleus accumbens of NR2A knockout mice reverses the loss of abstinence behaviors. The activation of CaMKII and increased expression of c-Fos protein in the brain of animals with naloxone-precipitated withdrawal syndrome are prevented by NMDA receptor antagonists, whereas the increased levels of extracellular glutamate are not prevented by them. These findings indicate that glutamatergic neurotransmission at the NMDA receptor site contributes to the development, expression and maintenance of opiate dependence, and suggest that NMDA receptor antagonists may be a useful adjunct in the treatment of opiate dependence.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalEuropean Journal of Pharmacology
Volume500
Issue number1-3 SPEC. ISS.
DOIs
Publication statusPublished - 01-10-2004
Externally publishedYes

Fingerprint

Opioid-Related Disorders
N-Methyl-D-Aspartate Receptors
Proto-Oncogene Proteins c-fos
Naloxone
Knockout Mice
Opiate Alkaloids
Glutamic Acid
Maintenance
Morphine Dependence
aspartic acid receptor
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Messenger RNA
Electroporation
Antisense Oligonucleotides
Nucleus Accumbens
Protein Subunits
Brain
Synaptic Transmission

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

@article{ef701d8e1e3946a78e0557bc11ac1962,
title = "Opiate physical dependence and N-methyl-D-aspartate receptors",
abstract = "The present review focused the involvement of N-methyl-d-aspartate (NMDA) receptors in morphine physical dependence. The increased levels of extracellular glutamate, NMDA receptor ζ subunit (NR1) mRNA, NMDA receptor ε1 subunit (NR2A) protein, phosphorylated Ca 2+/calmodulin kinase II (p-CaMKII) protein, c-fos mRNA, c-Fos protein, are observed in the specific brain areas of mice and/or rats showing signs of naloxone-precipitated withdrawal. In preclinical and clinical studies, a variety of NMDA receptor antagonists and pretreatment with an antisense oligonucleotide of the NR1 have been reported to inhibit the development, expression and/or maintenance of opiate physical dependence. In contrast to data obtained in adult animals, NMDA receptor antagonists are neither effective in blocking the development of opiate dependence nor the expression of opiate withdrawal in neonatal rats. In the NMDA receptor-deficient mice, the NR2A knockout mice show the marked loss of typical withdrawal abstinence behaviors precipitated by naloxone. The rescue of NR2A protein by electroporation into the nucleus accumbens of NR2A knockout mice reverses the loss of abstinence behaviors. The activation of CaMKII and increased expression of c-Fos protein in the brain of animals with naloxone-precipitated withdrawal syndrome are prevented by NMDA receptor antagonists, whereas the increased levels of extracellular glutamate are not prevented by them. These findings indicate that glutamatergic neurotransmission at the NMDA receptor site contributes to the development, expression and maintenance of opiate dependence, and suggest that NMDA receptor antagonists may be a useful adjunct in the treatment of opiate dependence.",
author = "Yukihiro Noda and Toshitaka Nabeshima",
year = "2004",
month = "10",
day = "1",
doi = "10.1016/j.ejphar.2004.07.017",
language = "English",
volume = "500",
pages = "121--128",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3 SPEC. ISS.",

}

Opiate physical dependence and N-methyl-D-aspartate receptors. / Noda, Yukihiro; Nabeshima, Toshitaka.

In: European Journal of Pharmacology, Vol. 500, No. 1-3 SPEC. ISS., 01.10.2004, p. 121-128.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Opiate physical dependence and N-methyl-D-aspartate receptors

AU - Noda, Yukihiro

AU - Nabeshima, Toshitaka

PY - 2004/10/1

Y1 - 2004/10/1

N2 - The present review focused the involvement of N-methyl-d-aspartate (NMDA) receptors in morphine physical dependence. The increased levels of extracellular glutamate, NMDA receptor ζ subunit (NR1) mRNA, NMDA receptor ε1 subunit (NR2A) protein, phosphorylated Ca 2+/calmodulin kinase II (p-CaMKII) protein, c-fos mRNA, c-Fos protein, are observed in the specific brain areas of mice and/or rats showing signs of naloxone-precipitated withdrawal. In preclinical and clinical studies, a variety of NMDA receptor antagonists and pretreatment with an antisense oligonucleotide of the NR1 have been reported to inhibit the development, expression and/or maintenance of opiate physical dependence. In contrast to data obtained in adult animals, NMDA receptor antagonists are neither effective in blocking the development of opiate dependence nor the expression of opiate withdrawal in neonatal rats. In the NMDA receptor-deficient mice, the NR2A knockout mice show the marked loss of typical withdrawal abstinence behaviors precipitated by naloxone. The rescue of NR2A protein by electroporation into the nucleus accumbens of NR2A knockout mice reverses the loss of abstinence behaviors. The activation of CaMKII and increased expression of c-Fos protein in the brain of animals with naloxone-precipitated withdrawal syndrome are prevented by NMDA receptor antagonists, whereas the increased levels of extracellular glutamate are not prevented by them. These findings indicate that glutamatergic neurotransmission at the NMDA receptor site contributes to the development, expression and maintenance of opiate dependence, and suggest that NMDA receptor antagonists may be a useful adjunct in the treatment of opiate dependence.

AB - The present review focused the involvement of N-methyl-d-aspartate (NMDA) receptors in morphine physical dependence. The increased levels of extracellular glutamate, NMDA receptor ζ subunit (NR1) mRNA, NMDA receptor ε1 subunit (NR2A) protein, phosphorylated Ca 2+/calmodulin kinase II (p-CaMKII) protein, c-fos mRNA, c-Fos protein, are observed in the specific brain areas of mice and/or rats showing signs of naloxone-precipitated withdrawal. In preclinical and clinical studies, a variety of NMDA receptor antagonists and pretreatment with an antisense oligonucleotide of the NR1 have been reported to inhibit the development, expression and/or maintenance of opiate physical dependence. In contrast to data obtained in adult animals, NMDA receptor antagonists are neither effective in blocking the development of opiate dependence nor the expression of opiate withdrawal in neonatal rats. In the NMDA receptor-deficient mice, the NR2A knockout mice show the marked loss of typical withdrawal abstinence behaviors precipitated by naloxone. The rescue of NR2A protein by electroporation into the nucleus accumbens of NR2A knockout mice reverses the loss of abstinence behaviors. The activation of CaMKII and increased expression of c-Fos protein in the brain of animals with naloxone-precipitated withdrawal syndrome are prevented by NMDA receptor antagonists, whereas the increased levels of extracellular glutamate are not prevented by them. These findings indicate that glutamatergic neurotransmission at the NMDA receptor site contributes to the development, expression and maintenance of opiate dependence, and suggest that NMDA receptor antagonists may be a useful adjunct in the treatment of opiate dependence.

UR - http://www.scopus.com/inward/record.url?scp=4644244793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644244793&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2004.07.017

DO - 10.1016/j.ejphar.2004.07.017

M3 - Review article

VL - 500

SP - 121

EP - 128

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3 SPEC. ISS.

ER -