Effects of Long-Term Treatment with Atorvastatin and Rosuaastatin on Active Avoidance Test in Intact Rats

Summary

Statins are widely used for treatment of hyperlipidemia. They have been shown to possess pleiotropic effects apart from their lipid-lowering activity - anti-inflammatory, immunomodulatory, and neuroprotective. Most studies suggest that statins can protect the brain against damage but it is not clear whether they improve cognitive function in patients without neuropathy. The aim of the present study was to investigate the effect of 3-month treatment with atorvastatin and rosuvastatin on learning and memory processes in rats without brain damage. Wistar rats were treated orally for 90 days with atorvastatin and rosuvastatin at a dose of 10 mg/kg b. w. in parallel with the vehicle-treated group. After that period, learning ability and memory retention was evaluated using an active avoidance test - automatic reflex conditioner (shuttle box). The learning session was carried out on 5 consecutive days. Memory retention test was performed on day 12. The following behavioral reactions were investigated: conditioned responses (avoidance), unconditioned responses (escapes), and intertrial crossings. We found increased number of conditioned responses in groups, treated with atorvastatin 10 mg/kg b.w., and with rosuvastatin 10 mg/kg b.w. during the learning session and on the memory retention test, as compared to the same-day control group. The atorvastatin-treated group showed an increased number of unconditioned responses on days 1 and 2, as compared to the control group. In the group treated with Rosuvastatin there was an increased number of escapes on days 1,2 and 4, as compared to the vehicle-treated group. Atorvastatin and rosuvastatin at a dose of 10 mg/kg b.w. improved processes of learning and memory retention after the 3-month treatment.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. van der Most PJ, Dolga A,Nijholt I, Luiten P, Eisel U. Statins: Mechanisms of neuroprotection. Prog Neurobiol. 2009;88(l):64-75.

  • 2. Masse I, Beordet R, Deplanque D, A1K, Richard F, Libersa et al. Lipid lowering drugs are associated with a slower cognitive decline in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2005; 76(12): 1624-9.

  • 3. Jick H, Zomberg GL, Jick S, Seshadri S, Drachman DA. Statins and the risk of dementia, The Lancet. 2000;356:1627-31.

  • 4. Bemick C, Katz R, Smith NL, Rapp S, Bhadelia R, Carlson M, et al. Statins and cognitive function in the elderly: the Cardiovascular Health Study. Neurology. 2005;65(9): 1388-94.

  • 5. Parle M, Singh N. Reversal of memory deficits by Atorvastatin and Simvastatin in Rats. Yakugaku Zasshi. 2007; 127(7): 1125-37.

  • 6. Evans MA, Golomb BA, Statin-associated adverse cognitive effects: survey results from 171 patients. Pharmacotherapy. 2009;29(7):800-l 1.

  • 7. Padala KP, Padala PR, Potter JF, Simvastatin-induced decline in cognition, Ann Pharmacother. 2006;40( 10): 1880-3.

  • 8. Kalonia H, Kumar P, Kumar A. Comparative neuroprotective profile of statins in quinolinic acid induced neurotoxicity in rats. Behav Brain Res. 2011;216(1): 220-8.

  • 9. Wang H, Lynch JR, Song P, Yang HJ, Yates RB, Mace B, et al. Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration and improve cerebral blood flow after experimental traumatic brain injury. Exp Neurol. 2007;206(1): 56-69.

  • 10. Ucak A, Onan B, Guler A, Sahin MA, KihqkayaO, Oztaș E, et al. Rosuvastatin, a new generation 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, reduces ischemia/reperfesion-induced spinal cord tissue injury in rats. Ann Vase Surg. 2011;25(5):686-95.

  • 11. Baytan SH, Alkanat M, Okuyan M, Ekinci M, Gedikli E, Ozeren M, et al. Simvastatin impairs spatial memory in rats at a specific dose level. Tohoku J Exp Med. 2008;214(4):341 -9.

  • 12. Baytan SH, Alkatan M, Ozeren M, Ekinci M, Akgun A. Fluvastatin alters psychomotor performance and daily activity but not the spatial memory in rats. Tohoku J Exp Med. 2006,209(4), 311-20.

  • 13. Douma TN, Borre Y, Hendriksen H, Olivier B, Oosting RS. Simvastatin improves learning and memory in control but not in olfactory bulbectomized rats. Psychopharmacology. 2011 ;216(4):537-44.

  • 14. Vaughan CJ. Prevention of stroke and dementia with statins: effects beyond lipid lowering. Am J Cardiol.2003;91(4A):23B-29B.

  • 15. Wang Q, Zengin A, Deng C, Li Y, Newell KA, Yang GY, et al. High dose of simvastatin induces hyperlocomotive and anxiolytic-like activities: the association with the upregulation of NMDA receptor binding in the rat brain. Exp Neurol. 2009;216( 1): 132-8.

  • 16. Magnusson KR, Cotman C W. Effects of aging on NMDAnand MK801 binding sites in mice. Brain Res. 1993 ;604( 1 -2) :334-7.

  • 17. Malenka RC, Nicoll RA. Long-term potentiation-a decade of progress? Science 1999; 285(5435): 1870-4.

OPEN ACCESS

Journal + Issues

Search