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Ferulic acid through mitigation of NMDA receptor pathway exerts anxiolytic-like effect in mouse model of maternal separation stress

  • Zahra Lorigooini , Ali Nouri , Faezeh mottaghinia , Shima Balali-Dehkordi , Elham Bijad , Saeid Habibian Dehkordi , Amin Soltani and Hossein Amini-Khoei EMAIL logo
Published/Copyright: May 6, 2020

Abstract

Background

Experiencing early-life stress plays an important role in the pathophysiology of anxiety disorders. Ferulic acid is a phenolic compound found in some plants which has several pharmacological properties. N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of mood disorders. In this study we aimed to assess the anxiolytic-like effect of ferulic acid in a mouse model of maternal separation (MS) stress by focusing on the possible involvement of NMDA receptors.

Methods

Mice were treated with ferulic acid (5 and 40 mg/kg) alone and in combination with NMDA receptor agonist/antagonist. Valid behavioral tests were performed, including open field test (OFT) and elevated plus maze test (EPM), while quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate gene expression of NMDA subunits (GluN2A and GluN2B) in the hippocampus.

Results

Findings showed that treatment of MS mice with ferulic acid increased the time spent in the central zone of the OFT and increased both open arm time and the percent of open arm entries in the EPM. Ferulic acid reduced the expression of NMDA receptor subunit genes. We showed that administration of NMDA receptor agonist (NMDA) and antagonist (ketamine) exerted anxiogenic and anxiolytic-like effects, correspondingly. Results showed that co-administration of a sub-effective dose of ferulic acid plus ketamine potentiated the anxiolytic-like effect of ferulic acid. Furthermore, co-administration of an effective dose of ferulic acid plus NMDA receptor agonist (NMDA) attenuated the anxiolytic-like effect of ferulic acid.

Conclusions

In deduction, our findings showed that NMDA, partially at least, is involved in the anxiolytic-like effect of ferulic acid in the OFT and EPM tests.

Acknowledgments

This study was supported by a research grant (NO: 1396-08-75-3431) from Shahrekord University of Medical Sciences, Shahrekord, Iran. The authors are thankful to Professor Mahmoud Rafieian- Kopaei, Dr, Mohammad Reza Hojati and Dr. Gholam Reza Mobini for their contribution to this study.

  1. Author contributions: Z. L: performed experiments and writing the manuscript; A. N and F. M and E. B and A. S: performed experiments; S. BD: writing the manuscript and data analysis; S. HD: data analysis and editing the manuscript H. A-K: study design, writing the manuscript.

  2. Research funding: This work was supported by a grant from Shahrekord University of Medical Sciences (SKUMS) with grant number of “3431”.

  3. Competing interests: The authors declare no conflicts of interest

  4. Informed consent: All the authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  5. Ethical approval: All experimental procedures in this study were approved by the Ethics Committee of Shahrekord University of Medical Sciences, Shahrekord, Iran (ethical number: IR.SKUMS.REC.1396.103), and NIH Guidelines for the Care and Use of Laboratory Animals, revised 2011.

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Received: 2018-09-15
Accepted: 2020-02-24
Published Online: 2020-05-06

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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