Involvement of the Nitric Oxide Pathway in the Anti-Depressant-Like Effects of Thalidomide in Mice Publisher Pubmed



Rostamian A^{1, 2} ; Gharedaghi A^{1, 2} ; Norouzijavidan A¹ ; Dehpour AR^{2, 3}
Source: Physiology and Behavior Published:2019

Abstract

Background: Thalidomide is a sedative/hypnotic agent that is currently used to treat patients suffering from multiple myeloma, myelodysplastic syndromes and erythema nodosum leprosum. Although previous studies have demonstrated that thalidomide possesses anti-depressant-like properties, the exact mechanism that thalidomide exerts this effect is not understood. In this study, we used two mouse models of depression and investigated the possible role of nitric oxide (NO), NO synthase (NOS) and inducible NOS (iNOS) in the ant-depressant-like effects of thalidomide. Methods: Male mice were injected with different doses of thalidomide intraperitoneally. In order to assess the anti-depressant-like properties of thalidomide, the immobility time of mice was assessed in the forced swimming test (FST) and tail suspension test (TST). Locomotor activity was assessed using the open-field test. To assess the role of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME, non-specific NOS inhibitor), aminoguanidine (selective iNOS inhibitor) or L-arginine (NO precursor) were administered intraperitoneally along with specific doses of thalidomide. Results: Thalidomide (10 mg/kg) significantly reduced immobility time in FST and TST. Aminoguanidine (50 mg/kg) and L-NAME (10 mg/kg) significantly augmented the anti-immobility effects of thalidomide (5 mg/kg). L-arginine (750 mg/kg) significantly inhibited the anti-immobility effects of thalidomide (10 mg/kg). None of the treatment groups demonstrated alteration of locomotor activity. Conclusion: Thalidomide exerts its anti-depressant-like effects through a mechanism dependent upon NO inhibition. © 2019 Elsevier Inc.