Behavioral and convulsant effects of the (S) enantiomer of the group I metabotropic glutamate receptor agonist 3,5-DHPG in mice

Neuropharmacology. 2005 May;48(6):779-87. doi: 10.1016/j.neuropharm.2005.01.017.


The purpose of the present studies was to investigate the behavioral and convulsant effects produced by the group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG). Administered i.c.v. to mice, (S)-3,5-DHPG produced a behavioral syndrome consisting of scratching and/or facial grooming, tremors, slow forelimb clonus, rearing, and falling that increased over the dose range of 10-400 nmol. The full syndrome, produced by 400 nmol of (S)-3,5-DHPG, was antagonized by the selective mGlu1 receptor antagonist LY456236 but not by the mGlu5 receptor antagonist MPEP or the mGlu2/3 receptor antagonist LY341495. The behaviors induced by the 400 nmol dose were not blocked by the NMDA receptor antagonist MK-801, but were attenuated by the non-NMDA receptor antagonists GYKI 52466 and NBQX, and the Ca2+ mobilization inhibitor dantrolene, but at motor-impairing doses. The scratching behaviors produced by 30 nmol of (S)-3,5-DHPG were antagonized by LY456236 but not by MPEP, LY341495 or MK-801. GYKI 52466 and dantrolene, but not NBQX, inhibited scratching at motor-impairing doses. Both 400 and 30 nmol of (S)-3,5-DHPG produced a generalized seizure as recorded by surface EEG electrodes. LY456236 blocked the seizures produced by 30 nmol but not by 400 nmol; dantrolene was ineffective in blocking seizures produced by either dose. The present findings suggest that (S)-3,5-DHPG produces an increase in excitation that is mediated by mGlu1 and non-NMDA receptors.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Behavioral Symptoms / chemically induced
  • Behavioral Symptoms / physiopathology*
  • Convulsants / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electroencephalography / drug effects
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Regression Analysis
  • Resorcinols / pharmacology*


  • Convulsants
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Resorcinols
  • 3,5-dihydroxyphenylglycine
  • Glycine