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Neurotoxicity of Methamphetamine

  • Living reference work entry
  • First Online:
Handbook of Neurotoxicity

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Abstract

Recreational use and consumption of the highly addictive psychostimulant methamphetamine is a serious public health problem worldwide. Recent estimates indicate that methamphetamine abuse has increased in the last decade and that only cannabis is used by a greater number of consumers. Despite its popularity, methamphetamine is a known neurotoxin that damages dopaminergic terminals in the striatum, as indicated by reductions in striatal levels of dopamine and its metabolites and a sustained decrease in the expression of markers for dopaminergic terminals such as TH and DAT. In addition, methamphetamine affects the cell bodies of these same dopaminergic neurons in the substantia nigra, resulting in cell loss. The mechanisms underlying dopaminergic neurotoxicity are the focus of intense research and knowledge in this area has expanded in recent decades. Evidence from previous studies points to dysregulation of dopamine, oxidative stress, DNA damage, and mitochondrial dysfunction as the main cause of methamphetamine neurotoxicity. The dopamine receptors D1 and D2 also play an important role in methamphetamine-induced neurotoxicity since inactivation of either receptor is neuroprotective against methamphetamine. Results from clinical research indicate that methamphetamine abusers have a higher risk of developing Parkinson’s disease; this is in keeping with results in laboratory animals and confirms the persistence of methamphetamine-induced dopaminergic damage. These findings suggest that neuroprotective strategies that are effective against methamphetamine-induced toxicity are also promising candidates for preventive therapy for Parkinson’s disease and other persistent dopaminergic injuries.

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Abbreviations

ATS:

Amphetamine type stimulants

D1R:

Dopamine D1 receptor

D1R−/−:

D1R knockout mice

D2R:

Dopamine D2 receptor

D2R−/−:

D2R knockout mice

DAT:

Dopamine transporter

DOPAC:

3,4-Dihydroxyphenylacetic acid

Gclc:

γ-cysteine ligase catalitic subunit

Gclm:

γ-cysteine ligase modulatory subunit

GPx:

Glutathione peroxidase

HVA:

Homovanillic acid

MDMA:

3,4-methylendioxymethamphetamine also called “ecstasy”

Nrf2:

Nuclear factor-erythroid 2-related factor 2

PD:

Parkinson’s Disease

ROS:

Reactive oxygen species

SNpc:

Substantia nigra pars compacta

TH:

Tyrosine hydroxylase

VMAT2:

Vesicular monoamine transporter

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Author notes

  1. Sara Ares-Santos and Noelia Granado contributed equally with all other contributors.

Authors and Affiliations

  1. Instituto Cajal, Consejo Superior de Investigaciones Científicas, CSIC, and CIBERNED, ISCIII, Madrid, Spain

    Rosario Moratalla, Sara Ares-Santos & Noelia Granado

Authors
  1. Rosario Moratalla
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  2. Sara Ares-Santos
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  3. Noelia Granado
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Correspondence to Rosario Moratalla .

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Editors and Affiliations

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

    Richard M. Kostrzewa

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Moratalla, R., Ares-Santos, S., Granado, N. (2022). Neurotoxicity of Methamphetamine. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_123-1

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  • DOI: https://doi.org/10.1007/978-3-030-71519-9_123-1

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