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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

The NMDA antagonist memantine blocks the expression and maintenance of morphine dependence

P Popik1, P Skolnick

  • 1Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. nfpopik@cyf-kr.edu.pl

Pharmacology, Biochemistry, and Behavior
|April 1, 1996
PubMed

Insights

Memantine, an N-methyl-D-aspartate (NMDA) antagonist, can block the expression and maintenance of morphine dependence in mice. Its efficacy is greatest in detoxified subjects, not those with established opioid dependence.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Opioid dependence is a significant public health concern.
  • N-methyl-D-aspartate (NMDA) receptors play a role in addiction.
  • Memantine is an NMDA receptor antagonist.

Purpose of the Study:

  • To investigate the efficacy of memantine in blocking the expression and maintenance of morphine dependence in a mouse model.
  • To differentiate the effects of memantine on the acute expression versus the established maintenance of opioid dependence.

Main Methods:

  • Morphine-dependent mice were challenged with naloxone to precipitate withdrawal symptoms (jumping behavior).
  • Memantine was administered before naloxone challenge to assess its effect on dependence expression.
  • Memantine was administered repeatedly during a withdrawal period to assess its effect on dependence maintenance.
  • The effects of memantine were compared to a competitive NMDA antagonist (NPC 17742) and glycine.

Main Results:

  • Memantine dose-dependently reduced naloxone-precipitated jumping, indicating it blocks the expression of morphine dependence.
  • The effect of memantine on dependence expression was reversed by glycine, supporting its role as an NMDA antagonist.
  • Repeated memantine administration during a 3-day withdrawal period abolished subsequent naloxone-precipitated jumping, suggesting it inhibits dependence maintenance.
  • Memantine did not affect the maintenance of established morphine dependence when administered concurrently with morphine.

Conclusions:

  • NMDA antagonists, like memantine, can inhibit the maintenance of opioid dependence, a distinct action from their acute effects on dependence expression.
  • Regimen-dependent effects suggest NMDA antagonists are more efficacious for preventing or treating withdrawal in detoxified individuals rather than those actively dependent.
  • These findings highlight the potential therapeutic utility of NMDA antagonists in opioid addiction treatment, particularly during the detoxification phase.

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