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Neurosci Lett. 2016 Jan 12;611:106-11. doi: 10.1016/j.neulet.2015.11.031. Epub 2015 Nov 24.

Lipopolysaccharide induced anxiety- and depressive-like behaviour in mice are prevented by chronic pre-treatment of esculetin.

Author information

1
Laboratory of Neuroscience, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India. Electronic address: niperkunj@gmail.com.
2
Laboratory of Neuroscience, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
3
Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
4
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.

Abstract

Inflammation and oxidative stress are involved in the pathophysiology of anxiety and depression. Esculetin (ESC), a coumarin derived potent antioxidant, also possessing anti-inflammatory and neuroprotective activity. This study investigated the effect of ESC in lipopolysaccharide (LPS)-induced anxiety- and depressive-like behaviour in mice. ESC (25 and 50mg/kg, p.o.) was administered daily for 14 days, and challenged with saline or LPS (0.83mg/kg; i.p.) on the 15th day. Behavioural paradigms such as elevated plus maze (EPM), open field test (OFT), forced swim test (FST) and tail suspension test (TST) were employed to assess anxiety- and depressive-like behaviour in mice post-LPS injection. Hippocampal cytokines, MDA and GSH level, and plasma corticosterone (CORT) were measured. ESC pre-treatment significantly (P<0.05) attenuated LPS-induced anxiety-like behaviour by modulating EPM and OFT parameters. Moreover, LPS-induced increase in immobility time in FST and TST were also prevented significantly (P<0.05) by ESC (50mg/kg). ESC pre-treatment ameliorated LPS-induced neuroinflammation by attenuating brain IL-1β, IL-6, TNF-α level, and oxidative stress as well as plasma CORT level. In conclusion, the results suggest that ESC prevented LPS-induced anxiety- and depressive-like behaviour which may be governed by inhibition of cytokine production, oxidative stress and plasma CORT level. The results support the potential usefulness of ESC in the treatment of psychiatric disorders associated with inflammation and oxidative stress.

KEYWORDS:

Anxiety; Depression; Esculetin; Lipopolysaccharide; Neuroinflammation; Oxidative stress

PMID:
26620836
DOI:
10.1016/j.neulet.2015.11.031
[Indexed for MEDLINE]

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