Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats

Neuropharmacology. 2002 Aug;43(2):181-7. doi: 10.1016/s0028-3908(02)00082-5.


Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of action of anxiolytic and antidepressant drugs. The involvement of group I mGlu receptors in anxiety and depression has also been proposed. In view of the recent discovery of anxiolytic- or antidepressant-like effects of acute injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective and brain penetrable mGlu5 receptor antagonist, we designed the present study to examine anxiolytic- and/or antidepressant-like effects of multiple administrations of this drug. The anxiolytic-like effects of MPEP were evaluated in rats using the conflict drinking test. The antidepressant-like effect was estimated using the rat olfactory bulbectomy model of depression. Seven subsequent injections of MPEP (1 mg/kg) significantly (by 320%) increased the number of shocks accepted during the experimental session in the Vogel test. MPEP given once daily at a dose of 10 mg/kg, restored the learning deficit of bulbectomized rats after 14 days of treatment, remaining without any effect in the sham-operated animals. N-methyl-D-aspartic acid (NMDA)-induced convulsions in mice were not affected by a single injection of MPEP (30 mg/kg) indicating that at this dose MPEP did not block NMDA receptors. The results indicate that the prolonged blockade of mGlu5 receptors exerts anxiolytic- and antidepressant-like effects in rats. No tolerance to anxiolytic-like action occurs. The previously mentioned results further indicate that antagonists of group I mGlu receptors may play a role in the therapy of both anxiety and depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / administration & dosage*
  • Antidepressive Agents / administration & dosage*
  • Anxiety / drug therapy
  • Avoidance Learning / drug effects*
  • Avoidance Learning / physiology
  • Depression / drug therapy
  • Male
  • Mice
  • Pyridines / administration & dosage*
  • Rats
  • Rats, Wistar


  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Pyridines
  • 6-methyl-2-(phenylethynyl)pyridine