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Stress-induced hyperthermia: effects of acute and repeated dosing of MPEP

Rebecca E Nordquist1, Sean Durkin, Georg Jaeschke

  • 1F. Hoffmann-La Roche Ltd., PRBD-N, Psychiatry Disease Area, CH-4070 Basel, Switzerland.

European Journal of Pharmacology
|June 1, 2007
PubMed

Insights

The mGluR5 antagonist MPEP shows anxiolytic effects in mice. Repeated MPEP treatment did not diminish its effectiveness in reducing stress-induced hyperthermia, suggesting potential for chronic anxiety treatment.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • The metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP exhibits anxiolytic properties in animal models.
  • Previous research indicates that MPEP's efficacy can vary with repeated administration, with tolerance developing in some anxiety models.

Purpose of the Study:

  • To investigate the anxiolytic efficacy of repeated MPEP administration in a mouse model.
  • To determine if tolerance develops to the effects of MPEP after daily treatment.

Main Methods:

  • Acute administration of MPEP (3, 10, or 30 mg/kg, p.o.) and repeated daily administration (30 mg/kg, p.o. for five days) were tested.
  • The stress-induced hyperthermia model in mice was used to assess anxiolytic effects.

Main Results:

  • MPEP demonstrated a dose-dependent inhibition of stress-induced hyperthermia following acute administration.
  • Following five daily treatments, MPEP at 30 mg/kg retained its efficacy in reducing stress-induced hyperthermia.

Conclusions:

  • MPEP maintains its anxiolytic activity even after repeated daily administration.
  • These findings support the potential of MPEP as an anxiolytic agent for chronic use in managing anxiety disorders.

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