Opioid antinociception, tolerance and dependence: Interactions with the N-methyl-D-aspartate system in mice

Linda A. Dykstra, Bradford D. Fischer, Rebecca E. Balter, Fredrick E. Henry, Karl T. Schmidt, Laurence L Miller

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

This study explored the involvement of N-methyl-D-aspartate (NMDA) in the effects of μ-opioid agonists. A hot-plate procedure was used to assess antinociception and tolerance in mice in which the NR1 subunit of the NMDA receptor was reduced [knockdown (KD)] to approximately 10%, and in mice treated with the NMDA antagonist, (-)-6-phosphonomethyl-deca-hydroisoquinoline-3- carboxylic acid (LY235959). The μ opioid agonists, morphine, l-methadone and fentanyl, were approximately three-fold less potent in the NR1 KD mice than in wild-type (WT) controls; however, the development of morphine tolerance and dependence did not differ markedly in the NR1 KD and the WT mice. Acute administration of the NMDA antagonist, LY235959, produced dose-dependent, leftward shifts in the morphine dose-effect curve in the WT mice, but not in the NR1 KD mice. Chronic administration of LY235959 during the morphine tolerance regimen did not attenuate the development of tolerance in the NR1 KD or the WT mice. These results indicate that the NR1 subunit of the NMDA receptor does not play a prominent role in μ opioid tolerance.

Original languageEnglish (US)
Pages (from-to)540-547
Number of pages8
JournalBehavioural Pharmacology
Volume22
Issue number5-6
DOIs
StatePublished - Sep 1 2011

Fingerprint

N-Methylaspartate
Opioid Analgesics
LY 235959
Morphine
N-Methyl-D-Aspartate Receptors
Morphine Dependence
Methadone
Fentanyl
Carboxylic Acids

Keywords

  • N-methyl-Daspartate antagonist
  • NR1 knockdown mouse
  • antinociception
  • hotplate procedure
  • l-opioids
  • tolerance
  • withdrawal

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Opioid antinociception, tolerance and dependence : Interactions with the N-methyl-D-aspartate system in mice. / Dykstra, Linda A.; Fischer, Bradford D.; Balter, Rebecca E.; Henry, Fredrick E.; Schmidt, Karl T.; Miller, Laurence L.

In: Behavioural Pharmacology, Vol. 22, No. 5-6, 01.09.2011, p. 540-547.

Research output: Contribution to journalArticle

Dykstra, Linda A. ; Fischer, Bradford D. ; Balter, Rebecca E. ; Henry, Fredrick E. ; Schmidt, Karl T. ; Miller, Laurence L. / Opioid antinociception, tolerance and dependence : Interactions with the N-methyl-D-aspartate system in mice. In: Behavioural Pharmacology. 2011 ; Vol. 22, No. 5-6. pp. 540-547.
@article{3de881550e7c434480f0882f25e5ceeb,
title = "Opioid antinociception, tolerance and dependence: Interactions with the N-methyl-D-aspartate system in mice",
abstract = "This study explored the involvement of N-methyl-D-aspartate (NMDA) in the effects of μ-opioid agonists. A hot-plate procedure was used to assess antinociception and tolerance in mice in which the NR1 subunit of the NMDA receptor was reduced [knockdown (KD)] to approximately 10{\%}, and in mice treated with the NMDA antagonist, (-)-6-phosphonomethyl-deca-hydroisoquinoline-3- carboxylic acid (LY235959). The μ opioid agonists, morphine, l-methadone and fentanyl, were approximately three-fold less potent in the NR1 KD mice than in wild-type (WT) controls; however, the development of morphine tolerance and dependence did not differ markedly in the NR1 KD and the WT mice. Acute administration of the NMDA antagonist, LY235959, produced dose-dependent, leftward shifts in the morphine dose-effect curve in the WT mice, but not in the NR1 KD mice. Chronic administration of LY235959 during the morphine tolerance regimen did not attenuate the development of tolerance in the NR1 KD or the WT mice. These results indicate that the NR1 subunit of the NMDA receptor does not play a prominent role in μ opioid tolerance.",
keywords = "N-methyl-Daspartate antagonist, NR1 knockdown mouse, antinociception, hotplate procedure, l-opioids, tolerance, withdrawal",
author = "Dykstra, {Linda A.} and Fischer, {Bradford D.} and Balter, {Rebecca E.} and Henry, {Fredrick E.} and Schmidt, {Karl T.} and Miller, {Laurence L}",
year = "2011",
month = "9",
day = "1",
doi = "10.1097/FBP.0b013e328348ed08",
language = "English (US)",
volume = "22",
pages = "540--547",
journal = "Behavioural Pharmacology",
issn = "0955-8810",
publisher = "Lippincott Williams and Wilkins",
number = "5-6",

}

TY - JOUR

T1 - Opioid antinociception, tolerance and dependence

T2 - Interactions with the N-methyl-D-aspartate system in mice

AU - Dykstra, Linda A.

AU - Fischer, Bradford D.

AU - Balter, Rebecca E.

AU - Henry, Fredrick E.

AU - Schmidt, Karl T.

AU - Miller, Laurence L

PY - 2011/9/1

Y1 - 2011/9/1

N2 - This study explored the involvement of N-methyl-D-aspartate (NMDA) in the effects of μ-opioid agonists. A hot-plate procedure was used to assess antinociception and tolerance in mice in which the NR1 subunit of the NMDA receptor was reduced [knockdown (KD)] to approximately 10%, and in mice treated with the NMDA antagonist, (-)-6-phosphonomethyl-deca-hydroisoquinoline-3- carboxylic acid (LY235959). The μ opioid agonists, morphine, l-methadone and fentanyl, were approximately three-fold less potent in the NR1 KD mice than in wild-type (WT) controls; however, the development of morphine tolerance and dependence did not differ markedly in the NR1 KD and the WT mice. Acute administration of the NMDA antagonist, LY235959, produced dose-dependent, leftward shifts in the morphine dose-effect curve in the WT mice, but not in the NR1 KD mice. Chronic administration of LY235959 during the morphine tolerance regimen did not attenuate the development of tolerance in the NR1 KD or the WT mice. These results indicate that the NR1 subunit of the NMDA receptor does not play a prominent role in μ opioid tolerance.

AB - This study explored the involvement of N-methyl-D-aspartate (NMDA) in the effects of μ-opioid agonists. A hot-plate procedure was used to assess antinociception and tolerance in mice in which the NR1 subunit of the NMDA receptor was reduced [knockdown (KD)] to approximately 10%, and in mice treated with the NMDA antagonist, (-)-6-phosphonomethyl-deca-hydroisoquinoline-3- carboxylic acid (LY235959). The μ opioid agonists, morphine, l-methadone and fentanyl, were approximately three-fold less potent in the NR1 KD mice than in wild-type (WT) controls; however, the development of morphine tolerance and dependence did not differ markedly in the NR1 KD and the WT mice. Acute administration of the NMDA antagonist, LY235959, produced dose-dependent, leftward shifts in the morphine dose-effect curve in the WT mice, but not in the NR1 KD mice. Chronic administration of LY235959 during the morphine tolerance regimen did not attenuate the development of tolerance in the NR1 KD or the WT mice. These results indicate that the NR1 subunit of the NMDA receptor does not play a prominent role in μ opioid tolerance.

KW - N-methyl-Daspartate antagonist

KW - NR1 knockdown mouse

KW - antinociception

KW - hotplate procedure

KW - l-opioids

KW - tolerance

KW - withdrawal

UR - http://www.scopus.com/inward/record.url?scp=80051942769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051942769&partnerID=8YFLogxK

U2 - 10.1097/FBP.0b013e328348ed08

DO - 10.1097/FBP.0b013e328348ed08

M3 - Article

C2 - 21712708

AN - SCOPUS:80051942769

VL - 22

SP - 540

EP - 547

JO - Behavioural Pharmacology

JF - Behavioural Pharmacology

SN - 0955-8810

IS - 5-6

ER -