Abstract
Rationale
Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects.
Objective
To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CF3SePB) in mice and the involvement of the serotonergic and noradrenergic systems.
Methods
Male Swiss mice were treated with CF3SePB (1–50 mg/kg, i.g.) and 30 min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CF3SePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100 mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1 mg/kg, s.c., a 5-HT1A receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist), GR110838 (0.1 mg/kg, i.p., a 5-HT4 receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenergic receptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenergic receptor antagonist) and propranolol (2 mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF3SePB (50 mg/kg, i.g.), and after 30 min of CF3SePB administration the FST was performed.
Results
CF3SePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT1A and 5-HT3 receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CF3SePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice.
Conclusion
This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.
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Data availability
Data sets generated during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We gratefully thank Universidade Federal de Pelotas (UFPEL), Universidade Federal da Fronteira Sul (UFFS) (Edital nº 121/GR/UFFS/2021), Coordenação de Aperfeiçoamento Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, grant numbers 21/2551-0000728-1 and 21/2551-0000614-5). B.G., C.F.B, and C.A.B. are recipients of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) fellowship.
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Conceptualization: C.S.P and C.A.B; Data curation: C.S.P., M.J.R., M.H.P., N.P.Z., N.E.B.K.; Formal analysis; C.S.P., M.J.R., M.H.P., N.P.Z., and N.E.B.K.; Funding acquisition: B.G., C.F.B. and C.A.B.; Investigation: C.S.P., M.J.R., M.H.P., N.P.Z., and N.E.B.K.; Methodology: C.S.P., M.J.R., M.H.P., N.P.Z., and N.E.B.K.; Project administration: C.S.P., B.G., C.F.B., and C.A.B.; Resources: B.G., C.F.B. and C.A.B.; Supervision: B.G., C.F.B. and C.A.B.; Validation: C.S.P., B.G., C.F.B., and C.A.B.; Visualization: C.S.P., B.G., C.F.B., and C.A.B. Roles/Writing - original draft: C.S.P., M.J.R., M.H.P., N.P.Z.: Writing - review & editing: B.G., C.F.B., and C.A.B.
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Pires, C.S., da Rocha, M.J., Presa, M.H. et al. N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide induces antidepressant-like effect in mice: involvement of the serotonergic system. Psychopharmacology (2024). https://doi.org/10.1007/s00213-024-06588-8
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DOI: https://doi.org/10.1007/s00213-024-06588-8