Face-washing behavior induced by the group I metabotropic glutamate receptor agonist (S)-3,5-DHPG in mice is mediated by mGlu1 receptor.
It is known for the non-selective group I metabotropic glutamate (mGlu) receptors agonist (S)-3,5-dihydroxyphenylglycine (S-3,5-DHPG) to cause convulsions, which are mediated by mGlu1 receptor. However, the behavioral changes other than convulsions caused by (S)-3,5-DHPG have not been well studied. The purpose of the present study was to explore the behavioral changes elicited by activation of group I mGlu receptors with (S)-3,5-DHPG and to clarify which, mGlu1 receptor or mGlu5 receptor, is responsible for such behavior. (S)-3,5-DHPG at doses of 3-30 nmol caused characteristic face-washing behavior. This behavioral change was inhibited by both the competitive mGlu1 receptor antagonists (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) and (S)-4-carboxyphenylglycine (S-4CPG) and the non-competitive mGlu1 receptor antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide (FTIDC), but not by the mGlu5 receptor antagonist 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), the mGlu2/3 receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), the mGlu2/3 receptor antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), the N-methyl-d-asparate (NMDA) receptor antagonist 5R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), or the competitive non-NMDA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX). These findings indicate that face-washing behavior is due to selective activation of mGlu1 receptor by (S)-3,5-DHPG, and that the face-washing behavior induced by (S)-3,5-DHPG in mice can be used for in vivo testing of the antagonistic potency of both competitive and non-competitive mGlu1 receptor antagonists.
Hikichi
Hirohiko
H
Pharmacology, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan. hirohiko_hikichi@merck.com
Iwahori
Yuki
Y
Murai
Takeshi
T
Maehara
Shunsuke
S
Satow
Akio
A
Ohta
Hisashi
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D012118:Resorcinols / Q000494:pharmacology*; D012640:Seizures / Q000523:psychology
D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine