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The antidepressant-like action of mGlu5 receptor antagonist, MTEP, in the tail suspension test in mice is serotonin dependent

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Abstract

Rationale

Numerous studies indicate the potential antidepressant actions of several mGlu5 receptor antagonists, including 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP). The explanation for the mechanism of these effects might be a key step in finding new antidepressant drugs (AD).

Objectives

The aim of the present study was to investigate the possible role of the serotonergic system in the antidepressant-like activity of MTEP in the tail suspension test (TST) in C57BL/6J mice, using selected antagonists of serotonergic receptors and by applying two different methods of serotonin (5-HT) depletion.

Results

The results of our studies showed that the mGlu5 receptor antagonist, MTEP, similar to the fluoxetine used as reference AD, did not induce antidepressant-like effects in mice pretreated with tryptophan hydroxylase inhibitor, para-chlorophenylalanine. On the other hand, MTEP worked as a potential AD in the TST in mice fed on a tryptophan-free (TRP-free) diet for 3 weeks. However, fluoxetine, which was used as a reference control was also active in this experiment, suggesting that a TRP-free diet was not sufficiently effective in reducing the 5-HT level. Furthermore, we showed that the 5HT2A/2C antagonist, ritanserin, yet not the 5-HT1A antagonist, WAY100635, 5HT1B antagonist, SB224289 or 5HT4 antagonist, GR125487, reversed the antidepressant-like effects of MTEP in the TST. Finally, a sub-effective dose of MTEP co-administered with a sub-effective dose of citalopram induced an antidepressant-like effect in the TST in mice.

Conclusion

The results of our studies suggest the involvement of serotonergic system activation in the antidepressant-like effects of the mGlu5 antagonist, MTEP, in the TST in mice.

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Acknowledgments

This work was supported by Funds for Statutory Activity of the Institute of Pharmacology Polish Academy of Sciences and by the grant POIG.01.01.02-12-004/09 “Depression-Methods-Therapy”, task. 3.7.

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Authors and Affiliations

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

    Agnieszka Pałucha-Poniewiera, Piotr Brański, Joanna M. Wierońska, Katarzyna Stachowicz, Anna Sławińska & Andrzej Pilc

  2. Jagiellonian University, Collegium Medicum, Michałowskiego 12, 31-126, Kraków, Poland

    Andrzej Pilc

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  1. Agnieszka Pałucha-Poniewiera
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  2. Piotr Brański
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  4. Katarzyna Stachowicz
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  5. Anna Sławińska
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  6. Andrzej Pilc
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Correspondence to Agnieszka Pałucha-Poniewiera.

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Pałucha-Poniewiera, A., Brański, P., Wierońska, J.M. et al. The antidepressant-like action of mGlu5 receptor antagonist, MTEP, in the tail suspension test in mice is serotonin dependent. Psychopharmacology 231, 97–107 (2014). https://doi.org/10.1007/s00213-013-3206-6

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