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Related Experiment Videos

NMDA receptors modulate morphine-induced hyperthermia.

Scott M Rawls1, Martin W Adler, John P Gaughan

  • 1Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA. smrawls28@hotmail.com

Brain Research
|August 23, 2003
PubMed
Summary
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NMDA receptor antagonists, LY 235959 and dextromethorphan, reduce morphine-induced hyperthermia in rats. These findings suggest NMDA receptors play a key role in mediating this morphine side effect.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Morphine's effects are modulated by NMDA receptor complexes.
  • Acute morphine administration increases extracellular glutamate and downregulates NMDA receptors, suggesting increased glutamatergic transmission.
  • Both morphine and glutamate can induce hyperthermia.

Purpose of the Study:

  • To investigate the role of NMDA receptors in mediating morphine-induced hyperthermia in male Sprague-Dawley rats.

Main Methods:

  • Rats received subcutaneous injections of morphine (0.1-15 mg/kg) to induce hyperthermia.
  • Pretreatment with NMDA antagonists LY 235959 or dextromethorphan.
  • Administration of LY 235959 after morphine to assess reversal effects.
  • Administration of LY 235959 with DAMGO, a selective mu-opioid agonist.

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Main Results:

  • Morphine induced dose-dependent hyperthermia peaking 45-60 minutes post-injection.
  • Pretreatment with LY 235959 or dextromethorphan attenuated morphine-induced hyperthermia.
  • Administering LY 235959 after morphine did not reverse hyperthermia.
  • LY 235959 reduced hyperthermia caused by DAMGO, indicating NMDA receptor activation maximizes mu receptor-induced hyperthermia.
  • Neither antagonist alone altered body temperature.

Conclusions:

  • NMDA receptors modulate morphine-induced hyperthermia.
  • Increased glutamatergic transmission likely maximizes hyperthermia evoked by morphine.