Nitric oxide mechanism in protective effect of imipramine and venlafaxine against acute immobilization stress-induced behavioral and biochemical alteration in mice

Frequent and persistent stressful events caused depressive illness. Stress is an aversive stimulus which disturbs physiological homeostasis and reflects a variety of biological systems. The present study was designed to investigate the nitric oxide mechanism in the protective effect of imipramine and venlafaxine against acute immobilization stress-induced behavioral and biochemical alterations in mice. Mice were immobilized for 6 h. Imipramine (10 and 20 mg/kg) and venlafaxine (5 and 10 mg/kg) were administered 30 min before subjecting the animals to acute stress. Behavioral tests (mirror chamber, actophotometer, tail flick test) and biochemical analysis (malondialdehyde level, nitrite, glutathione and catalase enzyme) were performed subsequently. Acute immobilization stress caused anxiety like behavior, analgesia, impaired locomotor activity and oxidative stress as compared to naive. Pretreatment with imipramine (10 and 20 mg/kg) and venlafaxine (5 and 10 mg/kg) significantly reversed immobilized stress-induced behavioral and biochemical alterations. l-arginine (100 mg/kg) pretreatment with imipramine (10 mg/kg) and venlafaxine (5 mg/kg) significantly attenuated the protective effect of imipramine and venlafaxine. However, l-NAME (10 mg/kg) and/or methylene blue (10 mg/kg) pretreatment with lower dose of imipramine and venlafaxine significantly potentiated their protective effects which were significant as compared to their effect per se respectively. Present study highlights the involvement of nitric oxide mechanism in the protective effect of imipramine and venlafaxine against acute immobilization-induced behavioral and biochemical alterations in mice.