title: A selective mGlu7 receptor antagonist MMPIP reversed antidepressant-like effects of AMN082 in rats.
abstract: Previous behavioural studies strongly indicated on potential antidepressant-like activity of mGlu7 positive allosteric modulator, AMN082 (N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride). However, the mechanism of action of this drug was not clear. Some recent data, showing possible off-target activities of AMN082 and its metabolites casted doubt on the role of mGlu7 receptor activation in the antidepressant-like activity of this compound. In the present study we used a selective mGlu7 receptor antagonist, MMPIP (6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one), to investigate the role of mGlu7 receptor blockade in the antidepressant action of AMN082 in the forced swim test (FST) in rats. We showed that MMPIP (10 mg/kg, i.p.) completely reversed AMN082 (8 mg/kg, i.p.)-induced behavioural effects, including decreased immobility time and increased swimming time, suggesting the crucial role of mGlu7 receptor activation in the antidepressant-like effects of AMN082 in the FST. On the other hand, our studies showed, that AMN082 (8 mg/kg, i.p.)-induced decrease in locomotor activity was not affected by MMPIP (10 mg/kg, i.p.), indicating on other, non-mGlu7 receptor-dependent mechanisms involved in changes in locomotor activity of rats after AMN082 administration.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland. nfpaluch@cyf-kr.edu.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pałucha-Poniewiera
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pilc
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013550:Swimming
chemical_list: C553164:6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazonolo(4,5-c)pyridin-4(5H)-one; D000928:Antidepressive Agents; D001559:Benzhydryl Compounds; D018691:Excitatory Amino Acid Antagonists; C507346:N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride; D011728:Pyridones; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7