Nitriergic Influence in the Compromised Antidepressant Effect of Fluoxetine in Stressed Mice

Objective: Investigation of possible nitriergic mechanism involved in the compromised antidepressant effect of fluoxetine in stressed mice.

Materials and methods: Male swiss albino mice were used in the present study. Mice were stressed by immobilization of 2hrs. Mice subjected to stress were considered as stressed mice and mice not subjected to stress were considered as unstressed mice. All the treatments were administered intraperitoneally (i.p.) in a fixed volume of 10 ml/kg and the depression like behavioral alterations in unstressed and stressed mice was measured by TST followed by FST. Nitrite levels were measured in brain homogenates to determine the possible involvement of nitriergic mechanism.

Results: Present study showed that the 2hrs immobilization significantly increased the immobility period of mice in both TST and FST, with the concurrent increase in the levels of nitrite in the brain of stressed mice as compared to the vehicle treated unstressed mice. Fluoxetine (FLX) (20 mg/kg, i.p.); pyrrolidine dithiocarbamate (PDTC) (100 mg/kg, i.p.) and methylene blue (MB) (100 mg/kg, i.p.) significantly reduced the immobility period of stressed mice in both TST and FST as compared to vehicle treated stressed mice. Pre-treatment with PDTC (100 mg/kg, i.p.) followed by the administration of FLX (20 mg/kg, i.p.) did not significantly alter the immobility period and nitrite levels as compared to the FLX (20 mg/kg, i.p.) treated stressed mice. Pre-treatment with MB (100 mg/kg, i.p.) followed by the administration of FLX (20 mg/kg, i.p.) did not significantly alter the immobility period of mice in TST, but significantly reduced the immobility period of mice in FST as compared to the FLX (20 mg/kg, i.p.) treated stressed mice. Also the pre-treatment with MB (100 mg/kg, i.p.) followed by the administration of FLX (20 mg/kg, i.p.) significantly reduced the nitrite levels as compared to the FLX (20 mg/kg, i.p.) treated stressed mice.

Conclusion: It has been concluded that the immobilization stress induced increase production of NO was involved in the compromised antidepressant effect of fluoxetine in stressed mice.