Anxiolytic-like effects of mGlu1 and mGlu5 receptor antagonists in rats.
The purpose of the present study was to compare anxiolytic activity of the metabotropic glutamate receptor 1 (mGlu) antagonist, EMQMCM ((3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and the mGlu5 receptor antagonist MTEP ([(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine) and MPEP (2-methyl-6-(phenylethynyl)pyridine) in animal models of anxiety. In the elevated plus maze, diazepam (1 mg/kg), but not the mGlu1 or mGlu5 receptor antagonists induced anxiolytic-like effects. Meanwhile, MTEP (2.5 and 5 mg/kg), EMQMCM (5 mg/kg), and diazepam (2 mg/kg) all significantly inhibited fear potentiated startle. In the contextual fear conditioning test, MTEP (1.25 and 2.5 but not 5 mg/kg) and EMQMCM (0.6 to 5 mg/kg) attenuated freezing responding. In the Geller-Seifter conflict test, MPEP (1 and 3 mg/kg), MTEP (3 mg/kg), chlordiazepoxide (10 and 20 mg/kg) and midazolam (1 mg/kg) all facilitated punished responding, while ECMQCM failed to produce any significant effects up to 3 mg/kg dose. To summarise, the present data further support a significant anxiolytic potential of group I mGlu receptor antagonists, while suggesting the effects of mGlu1 receptor antagonists may depend on the experimental procedure and may be qualitatively different from those of mGlu5 receptor antagonists.
Pietraszek
Małgorzata
M
Preclinical R&D, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany.
Sukhanov
Ilia
I
Maciejak
Piotr
P
Szyndler
Janusz
J
Gravius
Andreas
A
Wisłowska
Aleksandra
A
Płaźnik
Adam
A
Bespalov
Anton Y
AY
Danysz
Wojciech
W
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000517:prevention & control / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008874:Midazolam / Q000494:pharmacology; D011678:Punishment / Q000523:psychology; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology
C502015:(3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate; C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D014151:Anti-Anxiety Agents; D011725:Pyridines; D011804:Quinolines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1; D002707:Chlordiazepoxide; D003975:Diazepam; D008874:Midazolam