title: 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.affiliation: Neuroscience Research Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Barton
authors.forename: Harlan E
authors.initials: HE
authors.lastname: Shannon
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001526:Behavioral Symptoms / Q000139:chemically induced / Q000503:physiopathology*; D003292:Convulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012044:Regression Analysis; D012118:Resorcinols / Q000494:pharmacology*
chemical_list: D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine