title: Current understanding of methamphetamine-associated dopaminergic neurodegeneration and psychotoxic behaviors.
abstract: Clinical and preclinical studies have indicated that chronic methamphetamine (MA) use is associated with extensive neurodegeneration, psychosis, and cognitive impairment. Evidence from animal models has suggested a considerable role of excess dopamine or glutamate, oxidative stress, neuroinflammation, and apoptosis in MA-induced neurotoxicity, and that protein kinase Cδ might mediate the interaction among these factors. In addition, the relatively long-lasting and recurrent nature of MA psychosis has been reproduced in animals treated with various dosing regimens of MA, which have shown behavioral sensitization, sociability deficits, and impaired prepulse inhibition. Genetic predisposition as well as dopaminergic and glutamatergic alterations might be important in the development of MA psychosis. Neuroimaging studies have identified functional and morphological changes related to the cognitive dysfunction shown in chronic MA users. Failure in the task-evoked phosphorylation of extracellular signal-related kinase likely underlies MA-induced memory impairment. Recent progress has suggested certain roles of oxidative stress and neuroinflammation in the psychosis and cognitive deficits induced by repeated low doses of MA. This review provides a comprehensive description of pertinent findings from human and animal studies, with an emphasis on the current understanding of the underlying mechanisms of MA neuropsychotoxicity and its relevance to Parkinson's disease or schizophrenia.
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Shin
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea.
authors.forename: Duy-Khanh
authors.initials: DK
authors.lastname: Dang
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea.
authors.forename: The-Vinh
authors.initials: TV
authors.lastname: Tran
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea.
authors.forename: Hai-Quyen
authors.initials: HQ
authors.lastname: Tran
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 06974, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 466-8560, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Science, Toyoake, 470-1192, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea. kimhc@kangwon.ac.kr.
authors.forename: Hyoung-Chun
authors.identifier: http://orcid.org/0000-0003-0420-795X
authors.initials: HC
authors.lastname: Kim
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008694:Methamphetamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D004298:Dopamine
keywords: Cognitive impairment; Methamphetamine; Neurotoxicity; Psychosis; Underlying mechanism