The Behavioral Profile of the Potent and Selective mGlu5 Receptor Antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) in Rodent Models of Anxiety

Previous reports have demonstrated the anxiolytic effect of the potent and systemically active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) in rodents. Here, we present evidence for the anxiolytic activity of a novel mGlu5 receptor antagonist...

Full description

Saved in:

Bibliographic Details
Published in:	Neuropsychopharmacology Vol. 29; no. 11; pp. 1971 - 1979
Main Authors:	BUSSE, Chris S, BRODKIN, Jesse, TATTERSALL, David, ANDERSON, Jeffery J, WARREN, Noelle, TEHRANI, Lida, BRISTOW, Linda J, VARNEY, Mark A, COSFORD, Nicholas D. P
Format:	Journal Article
Language:	English
Published:	New York, NY Nature Publishing 01-11-2004 Nature Publishing Group
Subjects:	Animals Anxiety - drug therapy Anxiety - metabolism Biological and medical sciences Disease Models, Animal Dose-Response Relationship, Drug Male Medical sciences Mice Neuropharmacology Pharmacology. Drug treatments Pyridines - chemistry Pyridines - metabolism Pyridines - therapeutic use Rats Rats, Sprague-Dawley Rats, Wistar Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate - antagonists & inhibitors Receptors, Metabotropic Glutamate - metabolism Thiazoles - chemistry Thiazoles - metabolism Thiazoles - therapeutic use Metabotropic receptor metabotropic glutamate receptor 5 MTEP Tolerance Anxiety Models Glutamate receptor Antagonist Behavior Biological receptor
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Previous reports have demonstrated the anxiolytic effect of the potent and systemically active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) in rodents. Here, we present evidence for the anxiolytic activity of a novel mGlu5 receptor antagonist, 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), in rats and compare its profile to the benzodiazepine receptor agonist diazepam. MTEP occupied mGlu5 receptors in a dose-dependent manner with essentially full receptor occupancy at the highest dose tested (10 mg/kg, i.p.). At doses appropriate for mGlu5 receptor-mediated effects, MTEP significantly reduced fear-potentiated startle and increased punished responding in a modified Geller-Seifter conflict model consistent with an anxiolytic-like profile. In both models, the magnitude of the anxiolytic-like response was similar to that seen with diazepam. In contrast, MTEP decreased unpunished responding to a lesser extent than diazepam and had no effect on rotarod performance when administered either alone or in combination with ethanol. Repeated dosing with MTEP in this model eliminated the increase in punished responding observed with acute dosing. The present results suggest that mGlu5 receptor antagonists lack the side effects seen with benzodiazepines, such as sedation and ethanol interaction, and provide insight into a possible role for mGlu5 receptor antagonists in the modulation of mood disorders.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0893-133X 1740-634X
DOI:	10.1038/sj.npp.1300540