Melatonin synergizes with citalopram to induce antidepressant-like behavior and to promote hippocampal neurogenesis in adult mice

Authors

  • Gerardo Ramírez-Rodríguez,

    Corresponding author
    1. Division of Clinical Research, Laboratory of Neurogenesis, National Institute of Psychiatry “Ramón de la Fuente Muñiz”, México, D.F., México
    • Address reprint requests to Gerardo Ramírez-Rodríguez, Division of Clinical Research, Laboratory of Neurogenesis, National Institute of Psychiatry, Calzada México-Xochimilco No. 101, Colonia San Lorenzo Huipulco, Delegación Tlalpan, México, D.F. C.P. 14370 México.

      E-mail: gbernabe@imp.edu.mx

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  • Nelly Maritza Vega-Rivera,

    1. Division of Neurosciences Research, Laboratory of Neuropsychopharmacology, National Institute of Psychiatry “Ramón de la Fuente Muñiz”, México, D.F., México
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  • Julián Oikawa-Sala,

    1. Division of Clinical Research, Laboratory of Neurogenesis, National Institute of Psychiatry “Ramón de la Fuente Muñiz”, México, D.F., México
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  • Ariadna Gómez-Sánchez,

    1. Division of Clinical Research, Laboratory of Neurogenesis, National Institute of Psychiatry “Ramón de la Fuente Muñiz”, México, D.F., México
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  • Leonardo Ortiz-López,

    1. Division of Clinical Research, Laboratory of Neurogenesis, National Institute of Psychiatry “Ramón de la Fuente Muñiz”, México, D.F., México
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  • Erika Estrada-Camarena

    1. Division of Neurosciences Research, Laboratory of Neuropsychopharmacology, National Institute of Psychiatry “Ramón de la Fuente Muñiz”, México, D.F., México
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Abstract

Adult hippocampal neurogenesis is affected in some neuropsychiatric disorders such as depression. Numerous evidence indicates that plasma levels of melatonin are decreased in depressed patients. Also, melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behavior. In addition, antidepressants revert alterations of hippocampal neurogenesis present in models of depression following a similar time course to the improvement of behavior. In this study, we analyzed the effects of both, citalopram, a widely used antidepressant, and melatonin in the Porsolt forced swim test. In addition, we investigated the potential antidepressant role of the combination of melatonin and citalopram (MLTCITAL), its type of pharmacological interaction on depressive behavior, and its effect on hippocampal neurogenesis. Here, we found decreased immobility behavior in mice treated with melatonin (<14–33%) and citalopram (<17–30%). Additionally, the MLTCITAL combination also decreased immobility (<22–35%) in comparison with control mice, reflecting an antidepressant-like effect after 14 days of treatment. Moreover, MLTCITAL decreased plasma corticosterone levels (≤13%) and increased cell proliferation (>29%), survival (>39%), and the absolute number of -associated new neurons (>53%) in the dentate gyrus of the hippocampus. These results indicate that the MLTCITAL combination exerts synergism to induce an antidepressant-like action that could be related to the modulation of adult hippocampal neurogenesis. This outcome opens the opportunity of using melatonin to promote behavioral benefits and hippocampal neurogenesis in depression and also supports the use of the MLTCITAL combination as an alternative to treat depression.

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