Association of neurobehavioral changes with reduced blood and brain cholinesterase activities in mice treated with high doses of three statins

Studies have suggested pleiotropic effects of the hypolipidemic statins, with behavioral outcome in man and laboratory animals. Limited information is available on the neurobehavioral effects of statins in mice. This study examines changes in neurobehavioral performance and cholinesterase (ChE) activity in mice by high doses of statins (atorvastatin, simvastatin and rosuvastatin). Two hours after vehicle or statin dosing at 250, 500, 750 or 1000 mg/kg, orally, each mouse was subjected to 5-min open-field activity, negative geotaxis at 45º/ 60 seconds, 5-min head pocking and forced swimming. Plasma, erythrocyte and brain ChE activities were determined spectrophotometrically 2- and 24-h after oral dosing of statins at 500 and 1000 mg/kg. The statins variably, but dose-dependently and significantly delayed the latency to move in the open-field arena, decreased locomotion and rearing, reduced head-pocking and delayed the negative geotaxis performance. They significantly increased the duration of forced swimming and decreased the duration of immobility in the swimming tank. The statins significantly and dose-dependently decreased plasma, erythrocyte and brain ChE activities 2- and 24-h after dosing. The data suggest that high doses of statins differentially modulate the neurobehavioral outcome in mice in association with reduced plasma, erythrocyte and brain ChE activities.