Simvastatin Impairs Spatial Memory in Rats at a Specific Dose Level

Abstract

Statins, inhibitors of cholesterol synthesis, are used to prevent cardiovascular complications. Moreover, statins have been shown to influence some cognitive functions. The modulating effects of simvastatin, one member of the statin family, on memory-related neurotransmitters and neuronal structures have also been reported. We aimed to investigate the behavioral effects of long-term simvastatin application on daily activity, psychomotor performance and spatial memory using Sprague−Dawley rats. Simvastatin (10 or 30 mg/kg/day) was administered orally to rats, in parallel with a vehicle-treated group. Daily activity test results of both simvastatin groups were found similar to the vehicle group after five weeks of simvastatin or vehicle application. Psychomotor performance was measured with the rotarod test. After 6 weeks of simvastatin or vehicle application, the vehicle-treated group stayed on the rotarod device for a shorter time compared with both simvastatin-treated groups. Spatial memory was evaluated by the Barnes maze test. Four weeks of 10 mg/kg/day simvastatin application led to poorer scores on spatial memory compared to the vehicle group, but surprisingly, this effect was not seen in the 30 mg/kg/day group. Our results revealed that simvastatin administration had no significant effect on daily activity. Psychomotor performance test results suggested that simvastatin alters psychomotor behavior at higher nervous system levels. Spatial memory test results indicate that long-term simvastatin usage impairs spatial memory only at 10 mg/kg/day dose.