Correction: Computational and biological evidences on the serotonergic involvement of SeTACN antidepressant-like effect in mice.

[This corrects the article DOI: 10.1371/journal.pone.0187445.]

Computational and biological evidences on the serotonergic involvement of SeTACN antidepressant-like effect in mice

<div><p>A series of phenylselanyl-1<i>H</i>-1,2,3-triazole-4-carbonitriles with different substituents were screened for their binding affinity with serotonin transporter (SERT) and dopamine transporter (DAT) by docking molecular. 5-(4methoxyphenyl)-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-4-carbonitrile (SeTACN) exhibited the best conformation with SERT even higher than fluoxetine and serotonin, suggesting a competitive inhibition. SeTACN demonstrated additional affinity to other serotonergic receptors involved in antidepressant effects: 5HT_1a, 5HT_2a and 5HT₃. In another set of experiments, SeTACN led to significant reductions in the immobility time of mice submitted to forced swimming test (FST) in the dose range of 0.1- 20mg/kg, suggesting an antidepressant-like effect. The possible mechanism of action was investigated using serotonergic and dopaminergic antagonists. The antidepressant-like effect of SeTACN (0.1mg/kg i.g.) was prevented by the pretreatment with WAY100635 (a selective 5HT_1a antagonist), ketanserin (a 5HT2_a/c antagonist) and ondansetron (a selective 5ht₃ antagonist), PCPA (an inhibitor of serotonin synthesis) but not with SCH23390 (dopaminergic D₁ antagonist) and sulpiride (D₂ antagonist). Sub-effective dose of fluoxetine was able to potentiate the effects of a sub-effective dose of SeTACN in FST. None of the treatments affected locomotor activity in open field test (OFT). These results together, suggest that the SeTACN antidepressant-like effect is mediate, at least in parts, by serotonergic system.</p></div

Scores (kcal/mol) of docking results of phenylselanyl-1<i>H</i>-1,2,3-triazole-4-carbonitriles class of compounds in serotonin transporter (SERT) and dopamine transporter (DAT).

<p>Scores (kcal/mol) of docking results of phenylselanyl-1<i>H</i>-1,2,3-triazole-4-carbonitriles class of compounds in serotonin transporter (SERT) and dopamine transporter (DAT).</p

Chemical structure of class phenylselanyl-1<i>H</i>-1,2,3-triazole-4-carbonitriles compounds.

<p>Compound 1: 5-phenyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-4-carbonitrile; Compound 2: 5-(4-fluorophenyl)-1-(2-(phenylselanyl)phenyl)-1H- 1,2,3-triazole-4-carbonitrile; Compound 3: 5-(4-chlorophenyl)-1-(2-(phenylselanyl)phenyl)-1H- 1,2,3-triazole-4-carbonitrile; Compound 4: 5-(4-methoxyphenyl)-1-(2-(phenylselanyl)phenyl)-1H- 1,2,3-triazole-4-carbonitrile and Compound 5: 1-(2-(phenylselanyl)phenyl)-5-(p-tolyl)-1H-1,2,3- triazole-4-carbonitrile.</p

Experimental paradigms illustrating the drugs and compound administration followed by behavioral tests.

<p>(A) Antidepressant-like activity of 5-(4methoxyphenyl)-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-4-carbonitrile (SeTACN). (B) Evaluation of mechanism of action involved in antidepressant-like effect of SeTACN. (C) Synergic effect of the combined treatment with sub-effective doses of clinical antidepressants and SeTACN.</p

Computational and biological evidences on the serotonergic involvement of SeTACN antidepressant-like effect in mice - Fig 6

<p>Effect of pretreatment of mice with (A) SCH233390 (0.05 mg/kg, s.c., a dopaminergic D₁ receptor antagonist) and (B) sulpiride (50 mg/kg, i.p., a dopaminergic D₂ receptor antagonist) on the anti-immobility effect of SeTACN (0.1mg/kg, i.g) in the FST. Data are presented as the mean ± S.E.M. (***) P < 0.001 in comparison to the vehicle treated group.</p