Acute antidepressant and anxiolytic effects of simvastatin and its mechanisms in rats

Objective: The aim of this study is to investigate the antidepressant and anxiolytic effects of simvastatin in rats. Methods: Sixty-four male adult (8-9 weeks old) Sprague-Dawley rats (200-250 g) were used. The forced swimming test and the elevated plus maze test were used for testing the antidepressant and anxiolytic effects. Eight groups were formed: control (saline), simvastatin 10, 30, and 50 mg/kg, amitriptyline 10 mg/kg, sertraline 5 mg/kg, simvastatin 30 mg/ kg+amitriptyline 10 mg/kg, and simvastatin 30 mg/ kg+sertraline 5mg/kg combinations. The study was conducted at the Animal Experiment Laboratories, Department of Pharmacology, Eskisehir Osmangazi University Medical School, Eskisehir, Turkey from March to May 2010. Results: The immobility periods were significantly reduced by all doses of simvastatin. Simvastatin 10 and 30 mg/kg but not 50 mg/kg increased time spent in the open arm. A single dose of amitriptyline 10 mg/ kg showed significant antidepressant and anxiolytic effects. Sertraline 5 mg/kg showed significant antidepressant, but not anxiolytic effects. There was no change in the antidepressant and anxiolytic effects of simvastatin when combined with amitriptyline. A potentialization in antidepressant effect, and a decrease in anxiolytic effect of simvastatin were observed in combinations of simvastatin and sertraline. Conclusion: Simvastatin presents significant antidepressant and anxiolytic effects in rats similar to selective serotonin reuptake inhibitors, and interactions between the effects of simvastatin on indoleamine 2,3-dioxygenase enzymes, N-methyl- D-aspartic acid receptor blockade, and dopaminergic functions possibly mediate its antidepressant and anxiolytic effects.