The potential antidepressant-like effect of imidazoline I2 ligand 2-BFI in mice |
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Authors: | Tonello Raquel Villarinho Jardel Gomes da Silva Sant'Anna Gabriela Tamiozzo Lídia Machado Pablo Trevisan Gabriela Pinto Martins Marcos Antônio Ferreira Juliano Rubin Maribel Antonello |
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Institution: | 1. Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil;2. Programa de Pós-graduação em Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil;3. Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil |
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Abstract: | The compound 2-(2-benzofuranyl)-2-imidazoline (2-BFI) is a 2-imidazoline derivative that selectively inhibits the in vitro activity of monoamine oxidase-A and it is also an imidazoline I(2) agonist. However, the antidepressant potential of this compound and its mechanism of action have not been well defined. Therefore, in this study we investigated the antidepressant-like effect of 2-BFI in mice. 2-BFI (100 and 300μmol/kg, s.c.) significantly reduced the immobility time on the tail suspension test (TST) without changing locomotion in the open field test. The reduced the immobility time of 2-BFI (100μmol/kg, s.c.) was confirmed with the forced swimming test (FST). The antidepressant-like effect of 2-BFI (100μmol/kg, s.c.) in the TST was prevented by pretreatment with idazoxan (0.4μmol/kg, i.p., a I(2) site antagonist), methysergide (4μmol/kg, i.p., a non-selective serotonergic receptor antagonist) and haloperidol (0.1μmol/kg, i.p., a non-selective dopaminergic receptor antagonist). The anxiolytic effect of 2-BFI was also evaluated, using the elevated plus-maze test. 2-BFI (300μmol/kg, s.c.) was able to significantly increase the % of number of entries and the % of time spent in the open arms, indicating that it possesses an anxiolytic effect at high doses. In conclusion, these results suggest that the antidepressant-like effect of 2-BFI might involve serotonergic, dopaminergic and imidazoline systems, and then the imidazoline site could represent a new pharmacological target for the treatment of depression. |
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Keywords: | ANOVA analysis of variance BU224 2-(4 5-dihydroimidaz-2-yl)-quinoline BU226 2-(4 5-dihydroimidaz-2-yl)-isoquinoline DA dopamine FST forced swimming test MAO monoamine oxidase MAO-A monoamine oxidase-A NUQUIMHE Núcleo de Química de Heterociclos OFT open field test SNK Student-Newman–Keuls' TST tail suspension test 2-BFI 2-(2-benzofuranyl)-2-imidazoline 5-HT serotonin |
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