• Agnieszka Palucha, Kinga Klak, Piotr Branski, Herman van der Putten, Peter J Flor, and Andrzej Pilc.
• Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343, Krakow, Poland. nfpaluch@cyf-kr.edu.pl
• Psychopharmacology (Berl.). 2007 Nov 1;194(4):555-62.

RationaleBroad evidence indicates that modulation of the glutamatergic system could be an efficient way to achieve antidepressant activity. Metabotropic glutamate receptor (mGlu receptor) ligands seem to be promising agents to treat several central nervous system disorders, including psychiatric ones.ObjectivesThe aim of our study was to investigate potential antidepressant-like activity of the first, selective, and bio-available mGlu7 receptor agonist, AMN082 (N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride), in wild-type (WT) and mGlu7 receptor knock-out (KO) mice.Materials And MethodsThe forced swim test (FST) and the tail suspension test (TST) in mice were used to assess antidepressant-like activity of AMN082.ResultsWe found that AMN082, administered IP, induced a dose-dependent decrease in the immobility time of WT animals in the FST and TST, suggesting antidepressant-like potency of an mGlu7 receptor agonist. Moreover, AMN082 did not change the behaviour of mGlu7 receptor KO mice compared to WT littermates in the TST, while imipramine, used as a reference control, significantly reduced their immobility, indicating an mGlu7 receptor-dependent mechanism of the antidepressant-like activity of AMN082. However, at high doses, AMN082 significantly decreased spontaneous locomotor activity of both mGlu7 receptor KO mice and WT control animals, suggesting off-target activity of AMN082 resulting in hypo-locomotion.ConclusionsThese results strongly suggest that activation of the mGlu7 receptor elicits antidepressant-like effects.

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