title: Prolonged administration of antidepressant drugs leads to increased binding of [(3)H]MPEP to mGlu5 receptors.
abstract: Metabotropic glutamate 5 (mGlu5) receptors are functionally connected with NMDA receptors. The antidepressant activity of the NMDA receptor antagonist ketamine in both preclinical and clinical studies, along with the antidepressant-like activities of negative allosteric modulators (NAMs) of mGlu5, led us to investigate if prolonged administration of various antidepressant drugs or the mGlu5 NAM, MTEP, causes changes in mGlu5 receptor availability or protein expression or in expression of Homer proteins in the rat brain. Our results clearly show that prolonged treatment with antidepressants with various mechanisms of action (such as escitalopram, reboxetine, milnacipran, moclobemide and imipramine) or with MTEP led to significant increases in [(3)H]MPEP binding in homogenates of the hippocampus and/or cerebral cortex. Increases in mGlu5 expression were also observed, though they did not always parallel the increase in binding. The results indicate that adaptive up-regulation of mGlu5 receptors may be a common change induced by antidepressant drugs.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
authors.affiliation: Jagiellonian University Medical College, Faculty of Pharmacy, Department of Toxicology, Medyczna 9, PL 30-688 Kraków, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Pomierny-Chamioło
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland; Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmacobiology, Medyczna 9, PL 30-688 Kraków, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.affiliation: Jagiellonian University Medical College, Faculty of Pharmacy, Department of Toxicology, Medyczna 9, PL 30-688 Kraków, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Niedzielska
authors.affiliation: Jagiellonian University Medical College, Faculty of Pharmacy, Department of Toxicology, Medyczna 9, PL 30-688 Kraków, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pomierny
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pałucha-Poniewiera
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. Electronic address: nfpilc@cyf-kr.edu.pl.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pilc
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D020912:Moclobemide / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011869:Radioligand Assay; D017208:Rats, Wistar; D000077593:Reboxetine; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D014316:Tritium
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D009025:Morpholines; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D013844:Thiazoles; D015283:Citalopram; D014316:Tritium; C121465:6-methyl-2-(phenylethynyl)pyridine; D000077593:Reboxetine; D007099:Imipramine; D020912:Moclobemide
keywords: Escitalopram; Homer proteins; Imipramine; MTEP; Milnacipran; Moclobemide; Reboxetine; [(3)H]MPEP; mGlu5 receptors