Adverse neurobehavioral changes with reduced blood and brain cholinesterase activities in mice treated with statins

Abstract

Background and Aim: Pleiotropic effects of hypolipidemic statins with behavioral outcomes have been suggested in humans and laboratory animals. There is limited information on the neurobehavioral effects of statins in mice. The aim of the present study was to examine changes in neurobehavioral performance and cholinesterase (ChE) activity in mice after high doses of three commonly used statins (atorvastatin, simvastatin, and rosuvastatin). Materials and Methods: Two hours after vehicle (control) 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 an angle of 45°/60 s, 5 min head pocking, and forced swimming endurance. Plasma, erythrocyte, and brain ChE activities were determined spectrophotometrically 2 and 24 h after oral dosing of statins at 500 and 1000 mg/kg. Results: The statins variably, but dose-dependently and significantly (p < 0.05) delayed the latency to move in the open-field arena, decreased locomotion and rearing, reduced head pocking, and delayed negative geotaxis performance. However, statins significantly increased the duration of forced swimming and decreased the duration of immobility in the swimming tank. Statins significantly and dose-dependently decreased plasma, erythrocyte, and brain ChE activity 2 and 24 h after dosing. Plasma and brain ChE activities recovered by 5%–32.9% and 5.7%–14.4% 24 h later from the 2 h ChE values, respectively. Conclusion: High doses of statins differentially modulate neurobehavioral outcomes in mice in association with reduced plasma, erythrocyte, and brain ChE activity. Plasma or erythrocyte ChE may be used for biomonitoring of the adverse/ therapeutic effects of statins. Keywords: atorvastatin, head pocking, negative geotaxis, open-field activity, rosuvastatin, simvastatin, swimming endurance.