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

Psychopharmacology (Berl). 2014 Jan;231(1):97-107. doi: 10.1007/s00213-013-3206-6.

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, parachlorophenylalanine. 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 ofMTEP coadministered 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents*
  • Citalopram / pharmacology
  • Diet
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Fenclonine / pharmacology
  • Fluoxetine / pharmacology
  • Hindlimb Suspension / psychology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Piperidines / pharmacology*
  • Receptors, Kainic Acid / antagonists & inhibitors*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Thiazoles / pharmacology*
  • Tryptophan / deficiency

Substances

  • 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)piperidine
  • Antidepressive Agents
  • Excitatory Amino Acid Antagonists
  • Gluk1 kainate receptor
  • Piperidines
  • Receptors, Kainic Acid
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Thiazoles
  • Fluoxetine
  • Citalopram
  • Serotonin
  • Tryptophan
  • Fenclonine