Metabolic Brain Disease

, Volume 33, Issue 5, pp 1573–1584 | Cite as

The antioxidant gallic acid induces anxiolytic-, but not antidepressant-like effect, in streptozotocin-induced diabetes

  • Mariana Machado Pereira
  • Helen de Morais
  • Eldevan dos Santos Silva
  • Claudia Rita Corso
  • Eliana Rezende Adami
  • Rose Maria Carlos
  • Alexandra Acco
  • Janaina Menezes ZanoveliEmail author
Original Article


The physiopathology of anxiety or depression related to diabetes is still poorly understood. The treatment with antidepressant drugs is a huge challenge due to theirs adherence low rate and many adverse effects. Thus, the seeking for a better treatment for these associated diseases is of utmost importance. Given that the oxidative stress in different tissues occurs in diabetes and anxiety or depression as well, the antioxidant gallic acid becomes an interesting compound to be investigated. Thus, the effects of long-term treatment with gallic acid (0, 10, 20 and 40 mg/kg; gavage) were evaluated in diabetic (DBT) animals submitted to the elevated plus-maze (EPM), the light-dark transition (LDT) tests and modified forced swim test (mFST). Also, indirect parameters of oxidative stress, lipid peroxidation (LPO) and reduced glutathione (GSH) levels were evaluated in the hippocampus (HIP) and prefrontal cortex (PFC). The results showed that DBT animals presented a decrease in the spent time in the open arms, in the end arm exploration and head dips when evaluated in the EPM test; moreover, a decrease in the spent time in the lit compartment of LDT test was observed, suggesting an anxiogenic-like behavior. During the mFST, an increase in the mean counts of immobility and a decrease in the mean counts of swimming and climbing were observed, indicating a depressive-like behavior. These aversive behaviors were more pronounced when compared to normoglycemic (NGL) animals and streptozotocin-treated animals that not become DBT. In addition, DBT rats showed an increase in the oxidative stress parameters in the HIP and PFC that was reversed by the gallic acid treatment (lowest dose - 10 mg/kg), i.e., the treatment decreased the elevated LPO levels and increased the reduced GSH in the HIP and PFC. Also, gallic acid treatment was able to produce an anxiolytic-like effect in the EPM and LDT tests, but not antidepressant–like effect in the FST. Taken together, the results suggest that the antioxidant/neuroprotective effect of gallic acid treatment in HIP and PFC of DBT animals may be essential to the anxiolytic-like effect.


Diabetes Gallic acid Hippocampus Prefrontal cortex Oxidative stress 



HM, CRC and ERA are recipients of a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Author contributions

Janaína M Zanoveli proposed the study. Mariana M Pereira and Helen de Morais conducted the behavioral tests. Claudia R Corso, Eliana R Adami and Alexandra Acco were responsible for evaluating oxidative stress. Eldevan S Silva and Rosa M Carlos were responsible for the donation of gallic acid. All of the authors contributed to the data analysis and interpretation, wrote the manuscript and approved the final article.

Compliance with ethical standards

Conflicts of interest

All of the authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mariana Machado Pereira
    • 1
  • Helen de Morais
    • 1
  • Eldevan dos Santos Silva
    • 2
  • Claudia Rita Corso
    • 1
  • Eliana Rezende Adami
    • 1
  • Rose Maria Carlos
    • 2
  • Alexandra Acco
    • 1
  • Janaina Menezes Zanoveli
    • 1
    Email author
  1. 1.Department of Pharmacology, Biological Sciences BuildingFederal University of ParanáCuritiba-PRBrazil
  2. 2.Departamento de QuímicaUniversidade Federal de São CarlosSão CarlosBrazil

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