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Cocaine as a Neurotoxin

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Abstract

Cocaine is a widely abused psychostimulant drug, with sympathomimetic properties and intense euphoric effects. Cocaine and some of its toxic metabolites cross the blood–brain barrier and induce neurologic impairments, affecting primarily the prefrontal cortex and basal ganglia. In this review, we discuss the mechanisms involved in brain dysfunction induced by cocaine, focusing on pre- and postsynaptic changes in dopaminergic and glutamatergic neurotransmission, oxidative stress, and mitochondrial dysfunction. Neurotoxic effects of combinations of cocaine with other drugs are also discussed. In summary, cocaine neurotoxicity may underlie brain dysfunction in cocaine and polydrug abusers and may predispose the brain to neurodegeneration.

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Abbreviations

Ca2+ i :

Intracellular Ca2+ concentration

DAT:

Dopamine transporter

DAQ:

Dopamine quinone

DARPP32:

Dopamine- and cAMP-regulated neuronal phosphoprotein

DOPAC:

3,4-dihydroxyphenylacetic acid

DOPAL:

3,4-dihydroxyphenylacetaldehyde

ERK:

Extracellular-signal-regulated kinase

GPx:

Glutathione peroxidase

GSH:

Reduced glutathione

H2O2 :

Hydrogen peroxide

MAO:

Monoamine oxidase

MAPKK/MEK:

Mitogen-activated protein kinase kinase/extracellular signal-regulated kinase kinase

MDA:

Malondialdehyde

NMDA:

N-methyl-d-aspartate

O2 •− :

Superoxide anion

•OH:

Hydroxyl radical

PARP:

Poly (ADP-ribose) polymerase

PD:

Parkinson’s disease

PKA:

Protein kinase A

PP1:

Protein phosphatase 1

Ras-GRF-1:

Ras protein-specific guanine nucleotide-releasing factor 1

SOD:

Superoxide dismutase

VMAT:

Vesicular monoamine transporter

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Acknowledgments

The authors’ lab is funded by project PEst-C/SAU/LA0001/2013-2014 from Fundação para a Ciência e a Tecnologia (FCT), Portugal, co-financed by COMPETE (Programa Operacional Factores de Competitividade), QREN, and European Union (FEDER, Fundo Europeu de Desenvolvimento Regional). T.C.-O. holds a postdoctoral fellowship from FCT reference SFRH/BPD/34711/2007, co-financed by POPH (Programa Operacional Potencial Humano), QREN, and European Union.

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Authors and Affiliations

  1. Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal

    Teresa Cunha-Oliveira

  2. Center for Neuroscience and Cell Biology (CNC) and Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    A. Cristina Rego & Catarina R. Oliveira

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  1. Teresa Cunha-Oliveira
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  2. A. Cristina Rego
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  3. Catarina R. Oliveira
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Corresponding author

Correspondence to Teresa Cunha-Oliveira .

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Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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© 2014 Springer Science+Business Media New York

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Cunha-Oliveira, T., Rego, A.C., Oliveira, C.R. (2014). Cocaine as a Neurotoxin. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_81

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