Evaluation Of Antidepressant Activity Of Statins Alone And In Combination With Fluoxetine In Acute And Chronic Behavioural Models Of Depression.

ABSTRACT

Context To study the role of statins (Atorvastatin, Simvastatin, and Pravastatin) as novel pharmacological option in treatment of depression. Aim: To evaluate antidepressant activity of statins (HMG-CoA reductase inhibitor) in combination with Fluoxetine in acute and chronic forced swim test in rats. Design: An experimental animal study. Materials and methods: Male albino wistar rats of either sex with weight range 150-250 grams were used. Part 1 is Dose finding study in acute forced swim test with three doses of Atorvastatin (2.5 mg/kg, 5 mg/ kg, 10 mg/kg), Simvastatin (2.5 mg/kg, 5 mg/kg, 10 mg/kg), and Pravastatin (10 mg/kg, 20 mg/kg, 40 mg/ kg) each were done. Part 2 was conducted to study the effects of statins (Atorvastatin, Simvastatin, and Pravastatin) and Fluoxetine (10 mg/kg) per se and in combination, on immobility of rats in acute forced swim test were compared. In part 3 effects of statins (Atorvastatin, Simvastatin, and Pravastatin) and Fluoxetine per se and in combination on immobility of rats in chronic forced swim test were compared. Open field test was performed to discriminate between the general behavioural stimulation (false positives) and antidepressant effect of study drugs. All study drugs were given orally. In Part 2 & 3 maximum effective dose of statin from part 1 was utilised. Statistics ANOVA with post-hoc Tukeys test, significant effects were analyzed further using post hoc Newman-Keuls tests. Results: In part 1 of dose finding study most effective doses for Atorvastatin, Simvastatin and Pravastatin were 10 mg/kg, 10 mg/kg and 40 mg/kg respectively. In this part acute forced swim test showed, no statistically significant reduction in duration of immobility by any of the statins (Atorvastatin, Simvastatin, and Pravastatin) as compared to control. In Part 2 acute forced swim test, When combined with Fluoxetine, Atorvastatin (157.83 ± 10.51) and Simvastatin (167.66 ± 7.71) showed significant reduction in duration of