Evidence for the involvement of the monoaminergic system in the antidepressant-like effect of magnesium |
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Authors: | Chandra C. Cardoso,Kelly R. Lobato,Ricardo W. Binfaré ,Priscilla K. Ferreira,Angelo O. Rosa,Adair Roberto S. Santos,Ana Lú cia S. Rodrigues |
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Affiliation: | 1. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900, Florianópolis-SC, Brazil;2. Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900, Florianópolis-SC, Brazil |
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Abstract: | Literature data has shown that acute administration of magnesium reduces immobility time in the mouse forced swimming test (FST), which suggests potential antidepressant activity in humans. However, its mechanism of action is not completely understood. Thus, this study is aimed at investigating the antidepressant-like action of magnesium and the possible involvement of the monoaminergic system in its effect in the FST. The immobility time in the FST was significantly reduced by magnesium chloride administration (30–100 mg/kg, i.p.) without accompanying changes in ambulation when assessed in an open-field test. The pre-treatment of mice with NAN-190 (0.5 mg/kg, i.p. a 5-HT1A receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist), ritanserin (4 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ketanserin (5 mg/kg, a preferential 5-HT2A receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), haloperidol (0.2 mg/kg, i.p., a non selective dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D1 receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist) 30 min before the administration of magnesium chloride (30 mg/kg, i.p.) significantly prevented its anti-immobility effect in the FST. Moreover, the administration of sub-effective doses of fluoxetine (10 mg/kg, i.p., serotonin reuptake inhibitor), imipramine (5 mg/kg, i.p., a mixed serotonergic noradrenergic reuptake inhibitor), bupropion (1 mg/kg, i.p., dopamine reuptake inhibitor) was able to potentiate the action of sub-effective doses of magnesium chloride. In conclusion, the present study provides evidence indicating that the antidepressant-like effect of magnesium in the FST is dependent on its interaction with the serotonergic (5-HT1A and 5-HT2A/2C receptors), noradrenergic (α1- and α2- receptors) and dopaminergic (dopamine D1 and D2 receptors) systems. |
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Keywords: | ANOVA, analysis of variance 5-HT, serotonin FST, forced swimming test i.p., intraperitoneal NMDA, N-methyl-d-aspartate MAOi, monoamine oxidase inhibitor NAN-190, 1-(2-methoxyphenyl)-4[-(2-phthalimido)butyl] piperazine) PCPA, p-chlorophenylalanine methyl ester SCH23390, (R)-(+)-7 chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride SSRI, selective serotonin reuptake inhibitor WAY100635, N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridynyl) cyclohexanecarboxamide |
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