title: The effect of statins on performance in the Morris water maze in guinea pig.
abstract: Statins play a crucial role in reducing the risk of death from cardiovascular disease in millions of people worldwide. Recently, pharmacovigilance data has suggested that statin drugs may have rare but significant adverse psychiatric effects, such as amnesia, anxiety and even aggression. In order to investigate the effects of statins on cognitive function in an animal model, we studied the effect of 6 weeks of daily administration of oral simvastatin (1 mg/kg) or atorvastatin (0.5mg/kg) in guinea pig on performance in the Morris water maze (MWM). Animals were also re-tested in the MWM, 2 weeks after drug cessation, to test for any changes in performance as a result of drug de-challenge. Guinea pigs treated with either statin showed a significant (P<0.001) decrease in total cholesterol and low density lipoprotein-cholesterol (LDL-C), which remained partially reduced after the 2 week drug washout period. Guinea pigs receiving either statin did not show any difference in latency to reach the platform, nor any difference in total distance travelled during testing. Also, analysis of probe trials revealed no significant differences between drug and vehicle groups. However, both groups spent a significantly (P<0.01) greater proportion of time in the outer zone of the maze (indication of increased anxiety) and showed an increase in swimming speed (P<0.05) compared with the vehicle group. Differences between groups for swimming speed, and time spent in the outer zone, were not retained in the drug de-challenge phase. Our results show that low dose treatment with statins can induce mild but significant anxiety in guinea pigs.
authors: Department of Pharmacology & Toxicology, Otago School of Medical Sciences, University of Otago, PO Box 913, Dunedin 9054, New Zealand.
authors: Simran
authors: S
authors: Maggo
authors: David
authors: D
authors: Clark
authors: John C
authors: JC
authors: Ashton
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors