Anxiolytic-like activity of MGS0039, a selective group II mGlu receptor antagonist, is serotonin- and GABA-dependent

Katarzyna Stachowicz; Joanna Wierońska; Helena Domin; Shigeyuki Chaki; Andrzej Pilc

doi:10.1016/s1734-1140(11)70603-x

Anxiolytic-like activity of MGS0039, a selective group II mGlu receptor antagonist, is serotonin- and GABA-dependent

Pharmacol Rep. 2011;63(4):880-7. doi: 10.1016/s1734-1140(11)70603-x.

Authors

Katarzyna Stachowicz¹, Joanna Wierońska, Helena Domin, Shigeyuki Chaki, Andrzej Pilc

Affiliation

¹ Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. stachow@if-pan.krakow.pl

PMID: 22001975
DOI: 10.1016/s1734-1140(11)70603-x

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.

Publication types

Comparative Study

MeSH terms

Animals
Anti-Anxiety Agents / administration & dosage
Anti-Anxiety Agents / pharmacology*
Anxiety / drug therapy*
Anxiety / physiopathology
Bridged Bicyclo Compounds / administration & dosage
Bridged Bicyclo Compounds / pharmacology*
Diazepam / administration & dosage
Diazepam / pharmacology
Dicarboxylic Acids / administration & dosage
Dicarboxylic Acids / pharmacology*
Disease Models, Animal
Dose-Response Relationship, Drug
Male
Rats
Rats, Wistar
Receptors, GABA-A / drug effects
Receptors, GABA-A / metabolism
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Receptors, Serotonin / drug effects
Receptors, Serotonin / metabolism
Serotonin / metabolism

Substances

2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo(3.1.0)hexane-2,6-dicarboxylic acid
Anti-Anxiety Agents
Bridged Bicyclo Compounds
Dicarboxylic Acids
Receptors, GABA-A
Receptors, Metabotropic Glutamate
Receptors, Serotonin
metabotropic glutamate receptor 2
metabotropic glutamate receptor 3
Serotonin
Diazepam