Activation of the mGlu7 receptor elicits antidepressant-like effects in mice
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Broad 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.
The 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 methods
The forced swim test (FST) and the tail suspension test (TST) in mice were used to assess antidepressant-like activity of AMN082.
We 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.
These results strongly suggest that activation of the mGlu7 receptor elicits antidepressant-like effects.
KeywordsAntidepressant drugs AMN082 Forced swim test Locomotor activity mGlu7 receptor Tail suspension test
This work was partially supported by Polpharma Foundation for Pharmacy and Medicine Grant No.: 34/4/2006 to A Pilc and Funds for Statutory Activity of the Institute of Pharmacology Polish Academy of Sciences.
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