The effects of simvastatin on central dopaminergic systems

Abstract

Simvastatin(10 or 30 mg/kg/day 4 weeks) increased D1 and D2 receptors in the SD rat prefrontal cortex with no up-regulation in striatum. Simvastatin at 10mg/kg/day decreased dopamine in prefrontal cortex but increased in striatum with no change in dopamine re-uptake in both regions. Simvastatin (10 mg/kg/day) also increased eNOS in the prefrontal cortex but not nNOS or iNOS. The upregulation of D1 and D2 receptors was further demonstrated by functional studies involving the measurement of the second messenger cAMP after receptor activation and inhibition. D1/D2 also showed up-regulation in prefrontal cortex after 4 weeks treatment with simvastatin (10mg/kg/day) in eNOS knockout mice. The possibility of a nitric oxide mechanism involving eNOS requires further investigation. Among 6-OHDA lesioned PD rats, D1/D2 receptor in the prefrontal cortex decreased but restored to control levels after simvastatin treatment for 4 weeks. These findings may have implication in the treatment of cognitive decline in advanced PD.