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

Abstract

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.

• Authors: Matthew E Barton, Harlan E Shannon
• Journal: Neuropharmacology (Neuropharmacology) Vol. 48 Issue 6 Pg. 779-87 (May 2005) ISSN: 0028-3908 [Print] England
• PMID: 15829250 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

• Animals
• Behavior, Animal (drug effects)
• Behavioral Symptoms (chemically induced, 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, pharmacology)
• Male
• Mice
• Mice, Inbred ICR
• Regression Analysis
• Resorcinols (pharmacology)