The potential antidepressant-like effect of imidazoline I₂ ligand 2-BFI in mice

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• 作者：Raquel Tonello^a ; Jardel Gomes Villarinho^b ; Gabriela da Silva Sant'Anna^b ; Lí ; dia Tamiozzo^a ; Pablo Machado^c ; Gabriela Trevisan^a ; Marcos Antô ; nio Pinto Martins^c ; Juliano Ferreira^a ; ^b ; Maribel Antonello Rubin^a ; ^b ; ^{maribel.rubin@gmail.com}
• 关键词：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 ; Nú ; cleo de Quí ; mic
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：2012
• 期刊代码：222_02785846
• 类别：med
• 出版时间：27 April, 2012
• 卷：37
• 期：1
• 页码：15-21
• 文件大小：428 K

摘要

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 I₂ 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 300 渭mol/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 (100 渭mol/kg, s.c.) was confirmed with the forced swimming test (FST). The antidepressant-like effect of 2-BFI (100 渭mol/kg, s.c.) in the TST was prevented by pretreatment with idazoxan (0.4 渭mol/kg, i.p., a I₂ site antagonist), methysergide (4 渭mol/kg, i.p., a non-selective serotonergic receptor antagonist) and haloperidol (0.1 渭mol/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 (300 渭mol/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.