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Neurotoxicity of Methamphetamine

  • Reference work entry
  • First Online:
Handbook of Neurotoxicity

Abstract

Recreational consumption of the highly addictive psychostimulant methamphetamine is becoming 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 causes 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. Recent 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 injury. 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−/− :

D1R knockout mice

D1R:

Dopamine D1 receptor

D2R−/− :

D2R knockout mice

D2R:

Dopamine D2 receptor

DAT:

Dopamine transporter

DOPAC:

3,4-Dihydroxyphenylacetic acid

Gclm:

γ-Cysteine ligase modulatory subunit

Gclc:

γ-Cysteine ligase catalytic 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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    Authors and Affiliations

    1. Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), and CIBERNED, ISCIII, Avenida Doctor Arce 37, 28002, Madrid, Spain

      Rosario Moratalla, Sara Ares-Santos & Noelia Granado

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

      Richard M. Kostrzewa

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    Moratalla, R., Ares-Santos, S., Granado, N. (2014). Neurotoxicity of Methamphetamine. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_123

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