Taís da Silva Teixeira Rech1, Amália Gonçalves Alves1, Dianer Nornberg Strelow1, Letícia Devantier Krüger1, Luiz Roberto Carraro Júnior1, José Sebastião Dos Santos Neto2, Antonio Luiz Braga2, César Augusto Brüning3, Cristiani Folharini Bortolatto4. 1. Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBio), Laboratório de Bioquímica e Neurofarmacologia Molecular (LABIONEM), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas (UFPel), Pelotas, RS, CEP 96010-900, Brasil. 2. Programa de Pós-Graduação em Química (PPGQ), Laboratório de Síntese de Derivados de Selênio E Telúrio (LabSelen), Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brasil. 3. Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBio), Laboratório de Bioquímica e Neurofarmacologia Molecular (LABIONEM), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas (UFPel), Pelotas, RS, CEP 96010-900, Brasil. cabruning@yahoo.com.br. 4. Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBio), Laboratório de Bioquímica e Neurofarmacologia Molecular (LABIONEM), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas (UFPel), Pelotas, RS, CEP 96010-900, Brasil. cbortolatto@gmail.com.
Abstract
RATIONALE: Depression is a psychiatric disorder that constitutes one of the leading causes of disability worldwide. 2-Phenyl-3-(phenylselanyl)benzofuran (SeBZF1) has been studied as a potential antidepressant drug, but its pharmacological action needs more investigation. OBJECTIVES AND METHODS: Our aim was to extend information about the antidepressant-like action of SeBZF1 using the mouse tail suspension test (TST). Initial experiments investigated the mechanisms involved in the acute antidepressant-like action of SeBZF1 in male Swiss mice. For this purpose, males received noradrenergic or dopaminergic receptor antagonists before acute SeBZF1 administration (50 mg/kg, per oral). In parallel, effects of combined treatment with SeBZF1 and bupropion at sub-effective doses (1 and 3 mg/kg, respectively) were tested. The next experiments were designed to determine the acute effects of SeBZF1 in females through a dose-response curve (5-50 mg/kg). Lastly, the efficacy of a 7-day repeated treatment with SeBZF1 (1 and 5 mg/kg) in mice of both sexes and its safety were evaluated. TST and the open-field test (OFT) were employed in all behavioral experiments. RESULTS: Pre-administration of dopaminergic antagonists (SCH23390, a selective D1R antagonist; sulpiride, a selective D2/D3R antagonist; and haloperidol, a non-selective antagonist), but not of adrenergic α1, α2, and β-R antagonists, blocked the acute antidepressant-like effects of SeBZF1 in males. Co-administration of sub-effective doses of SeBZF1 and bupropion reduced the depressive phenotype. In addition, acute treatment with SeBZF1 at 50 mg/kg produced a reduction of female immobility. Finally, repeated treatment with SeBZF1 (1 and 5 mg/kg) was effective in causing antidepressant-like effects in both sexes. Locomotor activity, plasma transaminases, and urea levels remained unaltered after SeBZF1 exposure. CONCLUSION: Our findings provide evidence of the involvement of the dopaminergic system in the acutely antidepressant-like action of SeBZF1 in male mice and reveal the compound efficacy when acute or repeatedly administered in both sexes.
RATIONALE: Depression is a psychiatric disorder that constitutes one of the leading causes of disability worldwide. 2-Phenyl-3-(phenylselanyl)benzofuran (SeBZF1) has been studied as a potential antidepressant drug, but its pharmacological action needs more investigation. OBJECTIVES AND METHODS: Our aim was to extend information about the antidepressant-like action of SeBZF1 using the mouse tail suspension test (TST). Initial experiments investigated the mechanisms involved in the acute antidepressant-like action of SeBZF1 in male Swiss mice. For this purpose, males received noradrenergic or dopaminergic receptor antagonists before acute SeBZF1 administration (50 mg/kg, per oral). In parallel, effects of combined treatment with SeBZF1 and bupropion at sub-effective doses (1 and 3 mg/kg, respectively) were tested. The next experiments were designed to determine the acute effects of SeBZF1 in females through a dose-response curve (5-50 mg/kg). Lastly, the efficacy of a 7-day repeated treatment with SeBZF1 (1 and 5 mg/kg) in mice of both sexes and its safety were evaluated. TST and the open-field test (OFT) were employed in all behavioral experiments. RESULTS: Pre-administration of dopaminergic antagonists (SCH23390, a selective D1R antagonist; sulpiride, a selective D2/D3R antagonist; and haloperidol, a non-selective antagonist), but not of adrenergic α1, α2, and β-R antagonists, blocked the acute antidepressant-like effects of SeBZF1 in males. Co-administration of sub-effective doses of SeBZF1 and bupropion reduced the depressive phenotype. In addition, acute treatment with SeBZF1 at 50 mg/kg produced a reduction of female immobility. Finally, repeated treatment with SeBZF1 (1 and 5 mg/kg) was effective in causing antidepressant-like effects in both sexes. Locomotor activity, plasma transaminases, and urea levels remained unaltered after SeBZF1 exposure. CONCLUSION: Our findings provide evidence of the involvement of the dopaminergic system in the acutely antidepressant-like action of SeBZF1 in male mice and reveal the compound efficacy when acute or repeatedly administered in both sexes.
Authors: Ticiana Monteiro Abreu; Valdécio Silvano Monteiro; Ana Beatriz Souza Martins; Felipe Barros Teles; Renata Line da Conceição Rivanor; Érika Freitas Mota; Danielle S Macedo; Silvânia Maria Mendes de Vasconcelos; José Eduardo Ribeiro Honório Júnior; Norma Maria Barros Benevides Journal: Int J Biol Macromol Date: 2017-12-28 Impact factor: 6.953
Authors: Deniz Bagdas; Shakir AlSharari; Monzurul A Roni; Vera C Campbell; Pretal P Muldoon; F Ivy Carroll; M Imad Damaj Journal: Behav Brain Res Date: 2018-12-12 Impact factor: 3.332