GABAergic Influence in the Antidepressant Effect of Fluoxetine in Unstressed and Stressed Mice

Objective: To determine the influence of GABA in the antidepressant effect of fluoxetine in unstressed and stressed mice.

Materials and methods: Male swiss albino mice were used in the present study. Mice were stressed by immobilization for 2h. Mice subjected to immobilization were considered as stressed mice and mice not subjected to immobilization were considered as unstressed mice. Depression like behavioral alterations in unstressed and stressed mice was measured by tail suspension test (TST) followed by forced swim test (FST).

Results: The present study showed that the immobilization stress of 2h significantly enhanced the immobility period of mice in both TST and FST. Fluoxetine (FLX) (20 mg/kg, i.p.) significantly reduced the immobility period of both unstressed and stressed mice significantly as compared to their respective controls. Diazepam (DZP) (2 and 4 mg/kg, i.p.) significantly increased the immobility period of the unstressed mice whereas significantly reduced the immobility period of stressed mice in both TST and FST as compared to their respective controls. The combine treatment of DZP (2 mg/kg, i.p.) and FLX (20 mg/kg, i.p.) to the unstressed mice reduced the immobility period of unstressed mice in both TST and FST significantly as compared to the vehicle and DZP (2 mg/kg, i.p.) treated unstressed mice in TST. The co-administration of DZP (2 mg/kg, i.p.) and FLX (20 mg/kg, i.p.) before the immobilization of 2h significantly reduced the immobility period of stressed mice significantly as compared to the vehicle treated stressed mice in both TST and FST; whereas significantly as compared to the FLX (20 mg/kg, i.p.) treated stressed mice in TST only.

Conclusion: It has been concluded that the GABAergic influence is involved in the compromised antidepressant effect of the fluoxetine in stressed mice.