title: Anxiolytic-like activity of MGS0039, a selective group II mGlu receptor antagonist, is serotonin- and GABA-dependent.
abstract: In the present study, we examined the anxiolytic-like effects of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039), a mGluR2/3 antagonist, in the Vogel conflict drinking test in rats. MGS0039 administered at the doses of 1 and 2 mg/kg ip (yet not at 3 mg/kg) produced anxiolytic-like effects in this test. Diazepam (2.5-10 mg/kg) was used as a reference drug. In the second part of our experiment, MGS0039 was tested at an effective dose of 2 mg/kg after a mixed injection with ritanserin (5-HT(2A/C) receptor antagonist) and WAY100635 (5-HT(1A) receptor antagonist) or flumazenil (benzodiazepine receptor antagonist), and all of the compounds were found to attenuate the effect of MGS0039. The above results indicate that the mGluR2/3 antagonist MGS0039 may play a role in the therapy of anxiety and that its action may be mediated by serotonin and the GABAergic systems.
authors: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. stachow@if-pan.krakow.pl
authors: Katarzyna
authors: K
authors: Stachowicz
authors: Joanna
authors: J
authors: Wierońska
authors: Helena
authors: H
authors: Domin
authors: Shigeyuki
authors: S
authors: Chaki
authors: Andrzej
authors: A
authors: Pilc
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: C483757:2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo(3.1.0)hexane-2,6-dicarboxylic acid; D014151:Anti-Anxiety Agents; D001643:Bridged Bicyclo Compounds; D003998:Dicarboxylic Acids; D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate; D011985:Receptors, Serotonin; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D012701:Serotonin; D003975:Diazepam