Antidepressant-like effect of simvastatin in diabetic rats.

Diabetes mellitus is accompanied by hormonal and neurochemical changes that can be associated with anxiety and depression. I investigated the antidepressant effect of simvastatin (SMV) on diabetic rats. Rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were orally administered 0, 5, or 10 mg/kg of SMV daily for 14 days, then exposed to the forced swimming test (FST). Our results showed that diabetic rats had higher immobility duration than the CTR rats, and SMV decreased this depressive-like behavior in the diabetic rats. However, clomipramine lowered the immobility time in the CTR and STZ rats. STZ decreased serotonin concentration in the hippocampus, which was reversed by SMV and clomipramine. The dopamine concentration in the hippocampus decreased in the STZ groups compared with the CTR groups. However, SMV and clomipramine had no significant effect on the dopamine levels in either the CTR or STZ groups. Corticosterone levels were increased in the untreated STZ group; SMV and clomipramine significantly decreased corticosterone levels in the STZ groups, but had no effect on the CTR groups. In conclusion, SMV exerts an antidepressant-like effect on diabetic rats that are submitted to the FST. The antidepressant-like effect of SMV in the FST appears to be mediated, at least in part, by the biochemical changes to the blood levels of corticosterone and of serotonin concentration in the hippocampus.