Study of effects of donepezil and aspirin on working memory in rats using electroconvulsive shock model
Keywords:Aspirin, Donepezil, Electroconvulsive shocks, Working memory
Background: Memory is the most common cognitive ability lost with dementia commonly seen in Alzheimer’s disease (AD). Donepezil was the first cholinesterase inhibitor to be licensed in UK for AD. There is preliminary evidence that aspirin decreases the risk and delays the onset of AD. Low dose aspirin users had numerically lower prevalence of Alzheimer’s dementia and had better cognitive function than non-users.
Methods: Retention of conditioned avoidance response (CAR) was assessed by using repeated electroconvulsive shocks (ECS) in rats. Rats were divided into five groups: control (pretreated with distilled water), ECS (150 V, 50 Hz, with intensity of 210 mA for 0.5 sec) pretreated, combined aspirin (6.75 mg/kg) and pretreated ECS, combined donepezil (0.32 mg/kg) and pretreated ECS, combined aspirin, donepezil and pretreated ECS groups. Data were analyzed using the Chi-square test and ANOVA.
Results: Findings show that administration of ECS daily for 8 days results in transient amnesia and disruption of retention of CAR. Aspirin and donepezil administration significantly increased the retention of CAR in comparison to ECS. However, aspirin failed to show an increase in the retention of CAR as compared to donepezil. The combination of the two drugs showed statistically significant increase in the retention of CAR than either of these drugs given alone.
Conclusion: Neuroinflammation plays an important role in the pathophysiology of neurodegenerative disorder like AD. Combination of aspirin with donepezil increased the nootropic and neuroprotective effect of aspirin and thus may hold great clinical significance in such disorders.
Power AE, Vazdarjanova A, McGaugh JL. Muscarinic cholinergic influences in memory consolidation. Neurobiol Learn Mem. 2003;80(3):178-93.
Molino I, Colucci L, Fasanaro AM, Traini E, Amenta F. Efficacy of memantine, donepezil, or their association in moderate-severe Alzheimer’s disease: a review of clinical trials. Scientific World Journal. 2013;2013:925702.
Winblad B, Kilander L, Eriksson S, Minthon L, Båtsman S, Wetterholm AL, et al. Donepezil in patients with severe Alzheimer’s disease: double-blind, parallel-group, placebo-controlled study. Lancet. 2006;367(9516):1057-65.
Ghosh A, Dhumal VR, Tilak AV, Das N, Singh A, Bondekar AA. Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats. J Pharmacol Pharmacother. 2011;2(1):3-6.
Nilsson SE, Johansson B, Takkinen S, Berg S, Zarit S, McClearn G, et al. Does aspirin protect against Alzheimer’s dementia? A study in a Swedish population-based sample aged > or =80 years. Eur J Clin Pharmacol. 2003;59(4):313-9.
Desai KM, Bhavsar VH, Dhumal VR, Kelkar VV. Disruptive effects of repeated electroconvulsive shock on retention of learned active avoidance is attenuated by carbamazepine. IRCS Med Sci. 1983;11:516-7.6
Doody RS. Cholinesterase inhibitors and memantine: Best practices. CNS Spectr. 2008;13 10 Suppl 16:34-5.
Grammas P, Ovase R. Inflammatory factors are elevated in brain microvessels in Alzheimer’s disease. Neurobiol Aging. 2001;22(6):837-42.
Gomes I. Aspirin: a neuroprotective agent at high doses? Natl Med J India. 1998;11(1):14-7.
Persegani C, Russo P, Lugaresi E, Nicolini M, Torlini M. Neuroprotective effects of low-doses of aspirin. Hum Psychopharmacol. 2001;16(2):193-94.
Bruno PI, Vincenzo S, Francesco P. Are NSAIDs useful to treat Alzheimer’s disease or mild cognitive impairement? Front Aging Neurosci. 2010;2:1-14.