Possible Involvement of Nitric Oxide Signaling Pathway in the Protective Effect of Clomipramine Against Acute Immobilization Stress-Induced Behavioral and Biochemical Changes 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 clomipramine against acute immobilization stress-induced behavioral and biochemical alterations in mice.Methods: Mice were immobilized for 6h. Clomipramine (2.5, 5 and 10mg/kg) were administered 30min before subjecting the animals to acute stress. Behavioral tests (elevated plus maze, mirror chamber, locomotor activity) and biochemical analysis (brain glutamate, malondialdehyde (MDA), nitrite, glutathione (GSH) levels and glutathione peroxidase (GSH-Px) activity) were performed subsequently. Results: Acute immobilization stress caused anxiety-like behavior, impaired locomotor activity and oxidative stress as compared to naive. Pretreatment with clomipramine in the tested doses significantly reversed immobilization stress-induced behavioral and biochemical alterations. l-arginine (50mg/kg) pretreatment with clomipramine (5mg/kg) significantly attenuated the protective effect of clomipramine. However, l-NAME (10mg/kg) and/or methylene blue (10mg/kg) pretreatment with the same dose of clomipramine significantly potentiated their protective effects which were significant as compared to their effect per se respectively.Conclusions: Present study highlights the involvement of nitric oxide mechanism in the protective effect of clomipramine against acute immobilization-induced behavioral and biochemical alterations in mice.