Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT 2A/C Receptors.

Autor: Garcia CS; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., Besckow EM; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., da Silva Espíndola CN; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., D'Avila Nunes G; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., Zuge NP; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., de Azeredo MP; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., Rocha MJD; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., Carraro Junior LR; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., Penteado F; Laboratory of Clean Organic Synthesis (LASOL), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., Gomes CS; Laboratory of Clean Organic Synthesis (LASOL), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., Lenardão EJ; Laboratory of Clean Organic Synthesis (LASOL), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., Bortolatto CF; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil., Brüning CA; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box, 354, Pelotas, 96010-900 RS, Brazil.
Jazyk: angličtina
Zdroj: ACS chemical neuroscience [ACS Chem Neurosci] 2022 Jun 15; Vol. 13 (12), pp. 1746-1755. Date of Electronic Publication: 2022 May 23.
DOI: 10.1021/acschemneuro.2c00129
Abstrakt: The monoaminergic dysfunction plays a central role in major depressive disorder (MDD), a mental disturbance associated with constant feeling of sadness and lack of interest. The available treatments do not present a desirable efficacy and some of them provoke several adverse effects. In this context, organoselenium compounds and molecules containing the indolizine nucleus have demonstrated interesting pharmacological properties, including antidepressant-like effects. In this study, the antidepressant-like effect of 2-phenyl-1-(phenylselanyl)indolizine (SeI), a selenium-containing indolizine derivative, was investigated on the forced swimming test (FST) and on the tail suspension test (TST) in male Swiss mice. The involvement of the serotonergic system in this effect was also accessed. The selenium compound SeI (10-100 mg/kg, intragastrical (i.g.)) was administered 0.5 h before the behavioral tests, and it diminished the immobility on both FST and TST experiments, which is an indication of antidepressant-like effect. No changing in the locomotor motion was observed in the open-field test (OFT). The anti-immobility effect of SeI was not altered by the preadministration of the selective serotonergic receptor antagonists ondansetron (1 mg/kg, intraperitoneally (i.p.), antagonist of 5-HT 3 receptor) and WAY100635 (0.1 mg/kg, subcutaneous route (s.c.), antagonist of 5-HT 1A receptor). In contrast, the preadministration of ketanserin (1 mg/kg, i.p., antagonist of 5-HT 2A/C receptor) blocked this effect, demonstrating that the antidepressant-like effect of SeI involves 5-HT 2A/C . In addition, molecular docking studies showed a strong interaction between SeI and the receptors of 5-HT 2A and 5-HT 2C . The toxicological results demonstrated that SeI has low potential to cause adverse effects in mice. It was found that the antidepressant-like effect of SeI is related to modulation of the serotonergic system, and this selenium compound could be included in new treatment approaches for MDD.
Databáze: MEDLINE
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