[New perspectives on the mechanism of methamphetamine-induced neurotoxicity].
Various hypotheses have been proposed concerning the mechanisms responsible for methamphetamine (METH)-induced neurotoxicity including reactive oxygen species (ROS), dopamine quinones, glutamatergic activity, apoptosis, etc. Recently, new factors regarding glial cell line-derived neurotorophic factor, tumor necrosis factor-alpha, and alpha-synuclein contained in striatal interneural inclusions have also been associated with METH-induced neurotoxicity. In addition, METH-induced self-injurious behavior (SIB) has been proposed to be an acute or immediate behavioral marker predicting the long-lasting neurotoxicity induced by METH. Specifically, it has been proposed that the SIB response may accurately reflect the underlying mechanistic changes occurring in the neuron that eventually result in the long-lasting damage. Several studies have demonstrated that endogenous dopamine (DA) plays an important role in mediating METH-induced neuronal damage. DA release and redistribution from synaptic vesicles to cytoplasmic compartments is thought to involve METH-induced changes in both the vesicular monoamine transporter-2 and DA transporter function. In turn, the consequent elevation of cytosolic auto-oxidizable DA concentrations is thought generate ROS such as superoxide and hydroxyl radicals and cause the DA terminal injury. Finally, the inflammatory response of microglia and glutamatergic toxicity in astrocytes have been related to the METH-induced neurotoxicity. The objective of the present review will be to consolidate the new perspectives in an attempt to formulate a more cohesive explanation of the underlying mechanism responsible for METH-induced DA damage and its early biological markers.
Laboratory of Pharmacology, Kyushu Nutrition Welfare University Graduate School of Food and Nutrition, 5-1-1 Shimoitozu, Kokurakita-ku, Kitakyushu, 803-8511, Japan. kita@knwu.ac.jp
Taizo
T
Kita
Mika
M
Takeshima
George C
GC
Wagner
Hiroaki
H
Hozumi
Ikuko
I
Miyazaki
Masato
M
Asanuma
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects*; D016207:Cytokines / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000502:physiology; D005609:Free Radicals; D006801:Humans; D007249:Inflammation; D008694:Methamphetamine / Q000633:toxicity*; D017628:Microglia / Q000502:physiology; D018384:Oxidative Stress; D016728:Self-Injurious Behavior / Q000139:chemically induced*; D013378:Substantia Nigra / Q000187:drug effects*; D050493:Vesicular Monoamine Transport Proteins / Q000502:physiology; D051844:alpha-Synuclein / Q000502:physiology
D016207:Cytokines; D050483:Dopamine Plasma Membrane Transport Proteins; D005609:Free Radicals; D050493:Vesicular Monoamine Transport Proteins; D051844:alpha-Synuclein; D008694:Methamphetamine; D004298:Dopamine