Effect of co-administration of memantine and sertraline on the antidepressant-like activity and brain-derived neurotrophic factor (BDNF) levels in the rat brain

Meysam Amidfar, Gislaine Z. Réus, João Quevedo, Yong Ku Kim, Mohammad Arbabi

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    24 Citations (Scopus)


    A developing body of data has drawn attention to the N-methyl-D-aspartate (NMDA) receptor antagonists as potential drugs for the treatment of major depressive disorder (MDD). We investigated the possibility of synergistic interactions between the antidepressant sertraline with the uncompetitive NMDA receptor antagonist, memantine. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with memantine and sertraline alone or in combination in rats. To this aim, rats were chronically treated with memantine (2.5 and 5 mg/kg) and sertraline (5 mg/kg) for 14 days once a day, and then exposed to the forced swimming test. The brain-derived neurotrophic factor (BDNF) levels were assessed in the hippocampus and prefrontal cortex in all groups by ELISA sandwich assay. Sertraline and memantine (2.5 mg/kg) alone did not have effect on the immobility time; however, the effect of sertraline was enhanced by both doses of memantine. Combined treatment with memantine and sertraline produced stronger increases in the BDNF protein levels in the hippocampus and prefrontal cortex. Our results indicate that co-administration of antidepressant memantine with sertraline may induce a more pronounced antidepressant activity than treatment with each antidepressant alone. Antidepressant properties using the combination of memantine and sertraline could be attributed to increased levels of BDNF. This finding may be of particular importance in the case of drug-resistant patients and could suggest a method of obtaining significant antidepressant actions whereas limiting side effects.

    Original languageEnglish
    Pages (from-to)29-33
    Number of pages5
    JournalBrain Research Bulletin
    Publication statusPublished - 2017 Jan 1

    Bibliographical note

    Funding Information:
    The Translational Psychiatry Program (USA) is funded by the Department of Psychiatry and Behavioral Sciences , McGovern Medical School , The University of Texas Health Science Center at Houston (UTHealth) . Laboratory of Neurosciences (Brazil) is one of the centers of the National Institute for Molecular Medicine (INCT-MM) and one of the members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). Its research is supported by grants from CNPq (JQ) , FAPESC (JQ) ; Instituto Cérebro e Mente (JQ) and UNESC (JQ) . JQ is a 1A CNPq Research Fellow.

    Funding Information:
    This work was supported by the Tehran University of Medical Sciences.

    Publisher Copyright:
    © 2016 Elsevier Inc.


    • Brain-derived neurotrophic factor
    • Depression
    • Memantine
    • NMDA receptor
    • Rat brain

    ASJC Scopus subject areas

    • Neuroscience(all)


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