title: The antidepressant-like action of mGlu5 receptor antagonist, MTEP, in the tail suspension test in mice is serotonin dependent.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Agnieszka
authors: A
authors: Pałucha-Poniewiera
authors: Piotr
authors: P
authors: Brański
authors: Joanna M
authors: JM
authors: Wierońska
authors: Katarzyna
authors: K
authors: Stachowicz
authors: Anna
authors: A
authors: Sławińska
authors: Andrzej
authors: A
authors: Pilc
mesh_terms: D000818:Animals; D000928:Antidepressive Agents; D015283:Citalopram / Q000494:pharmacology; D004032:Diet; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D019417:Hindlimb Suspension / Q000523:psychology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D014364:Tryptophan / Q000172:deficiency
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D018691:Excitatory Amino Acid Antagonists; D010134:Fenclonine; D005473:Fluoxetine; D010880:Piperidines; D018092:Kainic Acid Receptors; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013844:Thiazoles; D014364:Tryptophan; C541428:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)piperidine
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