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Scopolamine-induced amnesia model: A possible anticholinergic mechanism with reversibility with statins and nootropic agents

Manas Ranjan Mishra, Niranjan Sahoo, Suresh Chandra Pradhan.


Background: High cholesterol turnover is implicated in the pathogenesis of Alzheimer’s disease by causing β amyloid plaque deposition and selective degeneration of cholinergic neurons in brain whereas drugs currently used for the treatment of the same are based on mechanisms which are cholesterol independent.

Aims and Objectives: The aim of the study is to find any cholesterol independent mechanisms such as antioxidant and cholinomimetic action of statins in a reversal of memory deficit in scopolamine-induced amnesia.

Materials and Methods: Sixty young Swiss albino mice were divided equally into 10 groups, i.e., Group I to Group X. Group I–V and Group VI–X were subjected two exteroceptive behavioral models, i.e., passive avoidance paradigm and Morris water maze, (MWM) respectively. Group I and Group VI served as negative control. Carboxymethyl cellulose (CMC), atorvastatin, simvastatin (test drugs), and piracetam (standard drug), respectively, were given orally to Group II and VII, Group III and VIII, Group IV and IX, and Group V and X for 14 days before inducing amnesia using scopolamine (0.4 mg/kg body weight) injection i.p.

Results: Step down latency of disease control group treated with CMC was significantly lower than that of the negative control group (42.5 ± 9.07 s vs. 147.5 ± 10.78 s) as well as that of statin and piracetam treated groups. Learning was good among all groups in MWM with a gradual decrease in escape latency from day 1 to day 4 but during memory retrieval test on day 5, CMC treated group performed poorly in comparison to others. There was no significant difference in plasma cholesterol levels among different groups whereas malondialdehyde was significantly lower among groups treated with statins or piracetam.

Conclusion: Statins reversed the scopolamine-induced amnesia by some cholesterol independent mechanisms.

Key words: Atorvastatin; Dementia; Memory; Malondialdehyde; Scopolamine; Simvastatin

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