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Rivastigmine reverses cognitive deficit and acetylcholinesterase activity induced by ketamine in an animal model of schizophrenia

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Abstract

Schizophrenia is one of the most disabling mental disorders that affects up to 1 % of the population worldwide. Although the causes of this disorder remain unknown, it has been extensively characterized by a broad range of emotional, ideational and cognitive impairments. Studies indicate that schizophrenia affects neurotransmitters such as dopamine, glutamate and acetylcholine. Recent studies suggest that rivastigmine (an acetylcholinesterase inhibitor) is important to improve the cognitive symptoms of schizophrenia. Therefore, the present study evaluated the protective effect of rivastigmine against the ketamine-induced behavioral (hyperlocomotion and cognitive deficit) and biochemical (increase of acetylcholinesterase activity) changes which characterize an animal model of schizophrenia in rats. Our results indicated that rivastigmine was effective to improve the cognitive deficit in different task (immediate memory, long term memory and short term memory) induced by ketamine in rats. Moreover, we observed that rivastigmina reversed the increase of acetylcholinesterase activity induced by ketamine in the cerebral cortex, hippocampus and striatum. However, rivastigmine was not able to prevent the ketamine-induced hyperlocomotion. In conslusion, ours results indicate that cholinergic system might be an important therapeutic target in the physiopathology of schizophrenia, mainly in the cognition, but additional studies should be carried.

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Abbreviations

ACh:

Acetylcholine

AChE:

Acetylcholinesterase

ChAT:

Choline acetyltransferase

ChEI:

Acetylcholinesterase inhibitors

CNS:

Central nervous system

NMDA:

N-Methyl-D-aspartate

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Financial Support

This Project was supported by L’Oreal, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Universidade do Extremo Sul Catarinense (UNESC) and FAPESC.

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Authors and Affiliations

  1. Laboratório de Neurociências, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), and Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil

    Alexandra I. Zugno, Ricardo Filipe Julião, Josiane Budni, Ana Maria Volpato, Daiane B. Fraga, Felipe D. Pacheco, Pedro F. Deroza, Renata D. Luca, Mariana B. de Oliveira, Alexandra S. Heylmann & João Quevedo

  2. Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil

    Alexandra I. Zugno

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  1. Alexandra I. Zugno
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  2. Ricardo Filipe Julião
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Correspondence to Alexandra I. Zugno.

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Zugno, A.I., Julião, R.F., Budni, J. et al. Rivastigmine reverses cognitive deficit and acetylcholinesterase activity induced by ketamine in an animal model of schizophrenia. Metab Brain Dis 28, 501–508 (2013). https://doi.org/10.1007/s11011-013-9417-z

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