The effects of rivastigmine plus selegiline on brain acetylcholinesterase, (Na⁺, K⁺)-, Mg²⁺-ATPase activities, antioxidant status, and learning performance of aged rats

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Authors: Haris Carageorgiou, Antonios C Sideris, Ioanna Messari, Chrissoula I Liakou, Stylianos Tsakiris

Published Date September 2008 Volume 2008:4(4) Pages 687 - 699

DOI: http://dx.doi.org/10.2147/NDT.S3272

Haris Carageorgiou¹, Antonios C Sideris¹, Ioanna Messari¹, Chrissoula I Liakou¹, Stylianos Tsakiris²

¹Department of Pharmacology, ²Department of Physiology, Medical School, University of Athens, Athens, Greece

Abstract: We investigated the effects of rivastigmine (a cholinesterase inhibitor) and selegiline ((-)deprenyl, an irreversible inhibitor of monoamineoxidase-B), alone and in combination, on brain acetylcholinesterase (AChE), (Na⁺, K⁺)-, Mg²⁺-ATPase activities, total antioxidant status (TAS), and learning performance, after long-term drug administration in aged male rats. The possible relationship between the biochemical and behavioral parameters was evaluated.

Methods: Aged rats were treated (for 36 days) with rivastigmine (0.3 mg/kg rat/day ip), selegiline (0.25 mg/kg rat/day im), rivastigmine plus selegiline in the same doses and way of administration as separately. Aged and adult control groups received NaCl 0.9% 0.5 ml ip.

Results: TAS was lower in aged than in adult rats, rivastigmine alone does not affect TAS, decreases AChE activity, increases (Na⁺, K⁺)-ATPase and Mg²⁺-ATPase activity of aged rat brain and improves cognitive performance. Selegiline alone decreases free radical production and increases AChE activity and (Na⁺, K⁺)-ATPase activity, improving cognitive performance as well. In the combination: rivastigmine seems to cancel selegiline action on TAS and AChE activity, while it has additive effect on (Na⁺, K⁺)-ATPase activity. In the case of Mg²⁺-ATPase selegiline appears to attenuate rivastigmine activity. No statistically significant difference was observed in the cognitive performance.

Conclusion: Reduced TAS, AChE activity and learning performance was observed in old rats. Both rivastigmine and selesiline alone improved performance, although they influenced the biochemical parameters in a different way. The combination of the two drugs did not affect learning performance.

Keywords: aged rat, brain enzymes, TAS, learning, rivastigmine, selegiline