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Related Experiment Videos

Decrease of tolerance to, and physical dependence on morphine by, glutamate receptor antagonists

P González1, P Cabello, A Germany

  • 1Department of Pharmacology, Faculty of Biological Sciences, University of Concepción, Chile.

European Journal of Pharmacology
|August 13, 1997
PubMed
Summary
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NMDA receptor antagonists, including dizocilpine and ketamine, were found to reduce morphine tolerance and physical dependence in mice. These compounds also lessened the severity of withdrawal symptoms, indicating a potential therapeutic role.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Opioid tolerance and physical dependence are significant challenges in pain management and addiction treatment.
  • The N-methyl-D-aspartate (NMDA) receptor is implicated in various forms of neuroplasticity, including those underlying opioid dependence.

Purpose of the Study:

  • To investigate the effects of NMDA receptor antagonists on the development and expression of morphine tolerance, physical dependence, and withdrawal syndrome in mice.
  • To determine if both competitive and non-competitive NMDA antagonists can modulate opioid-induced neuroadaptations.

Main Methods:

  • Mice received a single, slow-release dose of morphine.
  • Dizocilpine (non-competitive antagonist), ketamine (non-competitive antagonist), and CGP 39551 (competitive antagonist) were administered at various time points relative to morphine.

Related Experiment Videos

  • Tolerance, physical dependence, and naloxone-precipitated withdrawal were assessed.

    • Main Results:

    • Dizocilpine, ketamine, and CGP 39551 significantly reduced the intensity of morphine tolerance and physical dependence.
    • Administration of these NMDA antagonists also attenuated the expression of the morphine withdrawal syndrome.
    • Specific effective doses and administration timings were identified for each antagonist.

    Conclusions:

    • Both competitive and non-competitive NMDA receptor antagonists demonstrate efficacy in preventing morphine tolerance.
    • These antagonists decrease the development of physical dependence on opioids.
    • Targeting the NMDA receptor may offer a novel strategy for managing opioid tolerance and dependence.