title: Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption.
abstract: Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH-induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypothesis is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH-induced neurotoxicity has also been established including evidence of protection of bcl-2, expression of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3. The neuronal damage induced by METH may reflect neurological disorders such as autism and Parkinson's disease.
authors.affiliation: Department of Pharmacology, Nara Medical University, Nara, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Kita
authors.forename: George C
authors.initials: GC
authors.lastname: Wagner
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D012107:Research Design
chemical_list: D015306:Biogenic Monoamines; D008694:Methamphetamine