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Anhydroecgonine Methyl Ester (AEME), a Product of Cocaine Pyrolysis, Impairs Spatial Working Memory and Induces Striatal Oxidative Stress in Rats

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Abstract

When burning crack cocaine, the pyrolysis of cocaine generates anhydroecgonine methyl ester (AEME). AEME has been shown to be highly neurotoxic but its effects on cognitive function and oxidative stress are still unknown. Thus, this study investigated the effects of AEME on spatial working memory and on parameters of oxidative stress in the prefrontal cortex, hippocampus, and striatum. First, 18 well-trained rats in 8-arm radial maze (8-RM) procedures received acute intracerebroventricular (icv) administration of AEME at doses of 10, 32, or 100 μg or saline (SAL) in a counterbalanced order and were tested 5 min later in 1-h delayed tasks in the 8-RM. Secondly, separated animals received acute icv administration of AEME at doses of 10 (n = 5), 32 (n = 5), or 100 μg (n = 5) or SAL (n = 5) for analysis of advanced oxidation protein products, thiobarbituric acid, catalase, glutathione peroxidase, and superoxide dismutase. A higher number of errors were seen in the 1-h post-delay performance after AEME 32 μg and AEME 100 μg when compared to SAL. In the striatum, animals receiving AEME 100 μg icv showed increased advanced oxidation protein products levels when compared to 10 μg, and also showed increased activity of glutathione peroxidase enzyme when compared to SAL but also comparing to AEME 32 μg and AEME 10 μg. These results showed that AEME impairs long-term spatial working memory and also induces greater protein oxidation and increased levels of antioxidant enzymes in the striatum.

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Acknowledgements

We thank Professor Nyam Florencio da Silva from Federal University of Espírito Santo, the Laboratory of Molecular Histology and Immunohistochemistry (LHMI) from Federal University of Espírito Santo and the Civil Police Department of Espírito Santo State.

Funding

EMNP is a recipient of a researcher fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (proc. 304374/2014-8) and is also funded by this agency (proc. 466650/2014-0; 475232/2013-5 and 443824/2014-2) investigating the effects of brain stimulation in drug addiction. LCRM is funded by CNPq (proc. 456041/2014-1). EFG and IFSL were recipients of a graduate student fellowship from Espírito Santo Research Foundation FAPES (69923329) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), respectively.

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Correspondence to Ester Miyuki Nakamura-Palacios.

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Ethical Approval

All procedures performed in studies involving animals were in accordance with the ethical principles in animal experimentation (Brazilian College in Animal Experimentation—COBEA, revised, 2000). This project was submitted to the Commission on Ethics and Animal experimentation (CEUA) of CCS/UFES, approved under the number 10/2015.

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The authors declare that they have no conflict of interest.

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Gomes, E.F., Lipaus, I.F.S., Martins, C.W. et al. Anhydroecgonine Methyl Ester (AEME), a Product of Cocaine Pyrolysis, Impairs Spatial Working Memory and Induces Striatal Oxidative Stress in Rats. Neurotox Res 34, 834–847 (2018). https://doi.org/10.1007/s12640-017-9813-y

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  • DOI: https://doi.org/10.1007/s12640-017-9813-y

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