Methamphetamine neurotoxicity: Necrotic and apoptotic mechanisms and relevance to human abuse and treatment

Colin Davidson, Andrew J. Gow, Tong H. Lee, Everett H. Ellinwood

    Research output: Contribution to journalReview article

    388 Citations (Scopus)


    Research into methamphetamine-induced neurotoxicity has experienced a resurgence in recent years. This is due to (1) greater understanding of the mechanisms underlying methamphetamine neurotoxicity, (2) its usefulness as a model for Parkinson's disease and (3) an increased abuse of the substance, especially in the American Mid-West and Japan. It is suggested that the commonly used experimental one-day methamphetamine dosing regimen better models the acute overdose pathologies seen in humans, whereas chronic models are needed to accurately model human long-term abuse. Further, we suggest that these two dosing regimens will result in quite different neurochemical, neuropathological and behavioral outcomes. The relative importance of the dopamine transporter and vesicular monoamine transporter knockout is discussed and insights into oxidative mechanisms are described from observations of nNOS knockout and SOD overexpression. This review not only describes the neuropathologies associated with methamphetamine in rodents, non-human primates and human abusers, but also focuses on the more recent literature associated with reactive oxygen and nitrogen species and their contribution to neuronal death via necrosis and/or apoptosis. The effect of methamphetamine on the mitochondrial membrane potential and electron transport chain and subsequent apoptotic cascades are also emphasized. Finally, we describe potential treatments for methamphetamine abusers with reference to the time after withdrawal. We suggest that potential treatments can be divided into three categories; (1) the prevention of neurotoxicity if recidivism occurs, (2) amelioration of apoptotic cascades that may occur even in the withdrawal period and (3) treatment of the atypical depression associated with withdrawal.

    Original languageEnglish
    Pages (from-to)1-22
    Number of pages22
    JournalBrain Research Reviews
    Issue number1
    Publication statusPublished - 2001


    • Dopamine
    • Dosing regimen
    • Hyperthermia
    • Mitochondria
    • Reactive species
    • Treatments

    ASJC Scopus subject areas

    • Neuroscience(all)

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