Possible nitric oxide modulation in the protective effect of trazodone against sleep deprivation-induced anxiety like behavior and oxidative damage in mice

Abstract

Purpose: The present study was designed to explore the possible nitric oxide modulation in the protective effect of trazodone against sleep deprivation-induced behavioral alterations and oxidative damage in mice. Methods: In a controlled study, sleep deprivation was induced in 10 groups of mice (6 in each group) for 72 hr by using grid suspended over water method. Trazodone (5 and 10 mg/kg, ip), L-arginine (50 mg/kg, ip), L-NAME (10 mg/kg, ip) and methylene blue (10 mg/kg, i.p) were administered for 5 days, 2 days prior to the 72 hr sleep deprivation. Various behavioral tests (plus maze, zero maze, mirror chamber, actophotometer) followed by oxidative stress parameters (malondialdehyde level, reduced glutathione, catalase, nitrite and protein) were assessed in the animals. Results: The trazodone treatment significantly indcued anti-anxiety like effect, improved locomotor activity and antioxidant effect as indicated by reduced lipid peroxidation, nitrite concentration and restoration of depleted reduced glutathione and catalase activity. Further, prior treatment of the animals with L-NAME and methylene blue potentiated the protective effect of trazodone (5 mg/kg) (p<0.05). However, L-arginine combined with trazodone (5mg/kg) reversed the protective effect of trazodone (p<0.05). Conclusion: Results of present study suggest that NO modulation is involved in the protective effect of trazodone against sleep deprivation-induced anxiety like behavior and oxidative damage in mice. Keywords: Anxiety, locomotor activity, oxidative stress, sleep deprivation, trazodone, L-arginine, L-NAME, methylene blue.