Metabolic Brain Disease

, Volume 32, Issue 2, pp 401–413 | Cite as

Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice

  • Vishnu N. Thakare
  • Valmik D. Dhakane
  • Bhoomika M. PatelEmail author
Original Article


Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice. Swiss albino mice subjected to ARS exhibited an increased immobility time in forced swim test, elevated serum corticosterone and produced oxidative stress dependent alterations in cerebral cortex and hippocampus mainly increased thiobarbituric acid reactive substances and reduced catalase (CAT), superoxide dismutase (SOD) activity. Treatment with PCA was able to prevent stress induced immobility time in forced swim test without altering locomotor activity in mice. Further, PCA treatment attenuated the elevation of serum corticosterone, lipid peroxidation and restored enzymatic antioxidants in cerebral cortex and hippocampus in ARS mice. Altogether, the experimental findings demonstrate the notion that PCA exhibit antidepressant like activity might be related, at least in part, to its capability of modulating antioxidant defense system and oxidative damage induced by ARS in cerebral cortex and hippocampus in mice and thus maintain the pro−/anti-oxidative homeostasis.


Acute restraint stress Serum corticosterone Depressive like-behavior Hippocampal antioxidants Protocatechuic acid ethyl ester 



Authors are grateful to Prof. M. N. Navale, Founder President, Sinhgad Technical Education Society, Dr. R. N. Kane, Principal, and Rajesh R Patil, Sinhgad Institute of Pharmaceutical Sciences for providing necessary facilities, encouragement and support in the completion of present research studies.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Vishnu N. Thakare
    • 1
    • 2
  • Valmik D. Dhakane
    • 3
  • Bhoomika M. Patel
    • 2
    Email author
  1. 1.Department of PharmacologySinhgad Institute of Pharmaceutical SciencesLonavalaIndia
  2. 2.Department of Pharmacology, Institute of PharmacyNirma UniversityAhmedabadIndia
  3. 3.Research and Development, Astec Life SciencesMumbaiIndia

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