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Activation of the mGlu7 receptor elicits antidepressant-like effects in mice

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Abstract

Rationale

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.

Objectives

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.

Results

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.

Conclusions

These results strongly suggest that activation of the mGlu7 receptor elicits antidepressant-like effects.

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Acknowledgements

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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Authors and Affiliations

  1. Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343, Krakow, Poland

    Agnieszka Palucha, Kinga Klak, Piotr Branski & Andrzej Pilc

  2. Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland

    Herman van der Putten & Peter J. Flor

  3. Department of Drug Management, Collegium Medicum, Jagiellonian University, Krakow, Poland

    Andrzej Pilc

Authors
  1. Agnieszka Palucha
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  2. Kinga Klak
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  3. Piotr Branski
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  4. Herman van der Putten
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  5. Peter J. Flor
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  6. Andrzej Pilc
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Correspondence to Agnieszka Palucha.

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Palucha, A., Klak, K., Branski, P. et al. Activation of the mGlu7 receptor elicits antidepressant-like effects in mice. Psychopharmacology 194, 555–562 (2007). https://doi.org/10.1007/s00213-007-0856-2

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  • DOI: https://doi.org/10.1007/s00213-007-0856-2

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