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

• Published in: Neuropharmacology 2005-05, Vol.48 (6), p.779-787
• Main Authors: Barton, Matthew E., Shannon, Harlan E.
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Behavioral Symptoms - chemically induced; Behavioral Symptoms - physiopathology; Convulsants - pharmacology; DHPG; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography - drug effects; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Glutamate; Glycine - analogs & derivatives; Glycine - pharmacology; Male; Metabotropic receptors; mGlu1; Mice; Mice, Inbred ICR; Regression Analysis; Resorcinols - pharmacology; Seizures
• ISSN: 0028-3908; 1873-7064
• 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 Ca 2+ 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.