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

Abstract

Haris Carageorgiou1, Antonios C Sideris1, Ioanna Messari1, Chrissoula I Liakou1, Stylianos Tsakiris21Department of Pharmacology, 2Department of Physiology, Medical School, University of Athens, Athens, GreeceAbstract: 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