Possible Involvement of Nitric Oxide Signaling Pathway in the Protective Effect of Clomipramine Against Acute Immobilization Stress-Induced Behavioral and Biochemical Changes in Mice
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- Category: Vol. 79, September 2011
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Possible Involvement of Nitric Oxide Signaling Pathway in the Protective Effect of Clomipramine Against Acute Immobilization Stress-Induced Behavioral and Biochemical Changes in Mice BASEL A. ABDEL-WAHAB, M.D. and MOHAMED M. ELKHAWANKI, M.D.
Abstract
Frequent and persistent stressful events caused depressive illness. Stress is an aversive stimulus which disturbs physio-logical 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 biochem-ical alterations in mice.
Methods: Mice were immobilized for 6h. Clomipramine (2.5, 5 and 10mg/kg) were administered 30min before sub-jecting the animals to acute stress. Behavioral tests (elevated plus maze, mirror chamber, locomotor activity) and biochem-ical 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) signif-icantly 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 clomi-pramine against acute immobilization-induced behavioral and biochemical alterations in mice.