title: NMDA but not AMPA glutamatergic receptors are involved in the antidepressant-like activity of MTEP during the forced swim test in mice.
abstract: Several lines of evidence suggest an antidepressant-like activity for 3-[(methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP), a highly selective, non-competitive antagonist of metabotropic glutamate receptors subtype 5 (mGluR(5)). This effect has been observed following both acute and chronic MTEP treatments in behavioral tests and experimental models of depression, such as the forced swim test (FST), the tail suspension test, and the olfactory bulbectomy model of depression. However, the mechanism of action for mGluR(5) antagonists remains unclear. The aim of this study was to investigate whether the antidepressant-like action of MTEPis dependent on ionotropic glutamatergic receptors. Male Albino Swiss mice were used, and antidepressant-like activity was evaluated using the FST. The antidepressant-like effect of MTEP (0.3 mg/kg) was significantly antagonized by pre-treatment with the NMDA receptor agonist N-methyl-D-aspartic acid (NMDA, 75 mg/kg, i.p.). The AMPA receptor antagonist NBQX (10 mg/kg, i.p.) did not affect the MTEP activity. Our results indicate that the antidepressant-like activity of MTEP in the FST involves NMDA but not AMPA receptors and suggest that the interaction between mGluR(5) and NMDA receptors plays an important role in the underlying antidepressant mechanism(s).
authors.affiliation: Department of Toxicology, Jagiellonian University, Collegium Medicum, Medyczna 9, PL 30-688 Kraków, Poland. lpomiern@cm-uj.krakow.pl
authors.forename: Lucyna
authors.initials: L
authors.lastname: Pomierny-Chamioło
authors.forename: Ewa
authors.initials: E
authors.lastname: Poleszak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pilc
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D011725:Pyridines / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D013550:Swimming; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D011810:Quinoxalines; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013844:Thiazoles; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline