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

    374 Citations (Scopus)

    Abstract

    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
    Volume36
    Issue number1
    DOIs
    Publication statusPublished - 2001

    Fingerprint

    Methamphetamine
    Vesicular Monoamine Transport Proteins
    Reactive Nitrogen Species
    Dopamine Plasma Membrane Transport Proteins
    Mitochondrial Membrane Potential
    Electron Transport
    Primates
    Substance-Related Disorders
    Rodentia
    Reactive Oxygen Species
    Japan
    Necrosis
    Depression
    Apoptosis
    Pathology
    Research

    Keywords

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

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Methamphetamine neurotoxicity : Necrotic and apoptotic mechanisms and relevance to human abuse and treatment. / Davidson, Colin; Gow, Andrew J.; Lee, Tong H.; Ellinwood, Everett H.

    In: Brain Research Reviews, Vol. 36, No. 1, 2001, p. 1-22.

    Research output: Contribution to journalReview article

    Davidson, Colin ; Gow, Andrew J. ; Lee, Tong H. ; Ellinwood, Everett H. / Methamphetamine neurotoxicity : Necrotic and apoptotic mechanisms and relevance to human abuse and treatment. In: Brain Research Reviews. 2001 ; Vol. 36, No. 1. pp. 1-22.
    @article{c6072f599e3040828eb92c7e798f0b7a,
    title = "Methamphetamine neurotoxicity: Necrotic and apoptotic mechanisms and relevance to human abuse and treatment",
    abstract = "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.",
    keywords = "Dopamine, Dosing regimen, Hyperthermia, Mitochondria, Reactive species, Treatments",
    author = "Colin Davidson and Gow, {Andrew J.} and Lee, {Tong H.} and Ellinwood, {Everett H.}",
    year = "2001",
    doi = "10.1016/S0165-0173(01)00054-6",
    language = "English",
    volume = "36",
    pages = "1--22",
    journal = "Brain Research Reviews",
    issn = "0165-0173",
    publisher = "Elsevier",
    number = "1",

    }

    TY - JOUR

    T1 - Methamphetamine neurotoxicity

    T2 - Necrotic and apoptotic mechanisms and relevance to human abuse and treatment

    AU - Davidson, Colin

    AU - Gow, Andrew J.

    AU - Lee, Tong H.

    AU - Ellinwood, Everett H.

    PY - 2001

    Y1 - 2001

    N2 - 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.

    AB - 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.

    KW - Dopamine

    KW - Dosing regimen

    KW - Hyperthermia

    KW - Mitochondria

    KW - Reactive species

    KW - Treatments

    UR - http://www.scopus.com/inward/record.url?scp=0034882387&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0034882387&partnerID=8YFLogxK

    U2 - 10.1016/S0165-0173(01)00054-6

    DO - 10.1016/S0165-0173(01)00054-6

    M3 - Review article

    C2 - 11516769

    AN - SCOPUS:0034882387

    VL - 36

    SP - 1

    EP - 22

    JO - Brain Research Reviews

    JF - Brain Research Reviews

    SN - 0165-0173

    IS - 1

    ER -