Licofelone Attenuates LPS-induced Depressive-like Behavior in Mice: A Possible Role for Nitric Oxide

Seyyedeh Elaheh Mousavi1, Pegah Saberi2, Naeemeh Ghasemkhani3, Nahid Fakhraei3, Rezvan Mokhtari2, Ahmad Reza Dehpour4

1Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2Department of Pharmacology & Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
3Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
4Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Abstract


PURPOSE: Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, possesses antioxidant, antiapoptotic, neuroprotective, and anti-inflammatory properties. The aim of the present study was to investigate the effect of licofelone on lipopolysaccharide (LPS)-induced depression in a mouse model and also a possible role for nitric oxide (NO). METHODS: To elucidate the role of NO on this effect of licofelone (5 and 20 mg/kg, i.p.), L-NAME, a non-specific NO synthase (NOS) inhibitor; aminoguanidine (AG), a specific inducible NOS (iNOS) inhibitor; 7-nitroindazole (7-NI) a preferential neuronal NOS inhibitor (nNOS) and; L-arginine (L-Arg), as a NO donor, were used. The animal's behaviors were evaluated employing forced swimming test (FST), tail suspension test (TST) and open field test (OFT). RESULTS: LPS (0.83 mg/kg, i.p.) induced depressive-like behavior increasing immobility time in FST and TST. Conversely, licofelone (20 mg/kg i.p.) reversed the depressive effect of LPS and lowered the immobility time in FST and TST. On the other hand, pretreatment with L-Arg also reversed the antidepressant-like effect of licofelone (20 mg/kg) in FST and TST. On the other hand, L-NAME (10 and 30 mg/kg), AG (50 and 100 mg/kg) and 7-NI (60 mg/kg) could potentiate licofelone (5 mg/kg) and lowered the immobility duration. CONCLUSIONS: NO down-regulation possibly through iNOS and nNOS inhibition may involve in the antidepressant property of licofelone.

 

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J Pharm Pharm Sci, 21 (1): 184-194, 2018

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DOI: http://dx.doi.org/10.18433/jpps29770