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Cocaine as a Neurotoxin

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Handbook of Neurotoxicity

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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. This review discusses 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

DAQ:

Dopamine quinone

DARPP32:

Dopamine- and cAMP-regulated neuronal phosphoprotein

DAT:

Dopamine transporter

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’ laboratories are funded by the European Regional Development Fund (ERDF), through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia – under projects PTDC/BTM-SAL/29297/2017-POCI-01-0145-FEDER-029297, DL 57/2016/CP1448/CT0016, LA/P/0058/2020, and UIDB/04539/2020.

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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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Correspondence to Teresa Cunha-Oliveira .

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  1. Department of Biomedical Sciences, Quillen College of Medicine East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Cunha-Oliveira, T., Rego, A.C., Oliveira, C.R. (2022). Cocaine as a Neurotoxin. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-031-15080-7_81

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