title: Cardiotoxicity of methamphetamine under stress conditions: comparison of single dose and long-term use.
abstract: Methamphetamine (METH) abuse continues to be a worldwide problem, damaging the myocardial tissues, as well as the brains of individual users. In addition, stressors that increase drug cravings also contribute to cardiovascular diseases. The aim of the present study was to examine the myocardial effects of METH, including METH‑stress interactions and particularly, the effect of METH RNA expression in the heart. The study also aimed to compare single dose (acute) and long-term (chronic) treatments. Mice were divided into the control (C), METH injection (M), stress exposure (S) and METH plus stress (MS) groups and subjected to an acute water‑immersion restraint stress or a mixed chronic stress composed of restraint, electric foot‑shock and temperature change. METH was injected at 30 mg/kg (the acute study) or 10 mg/kg intraperitoneally (i.p.) three times per week (the chronic study). The results demonstrated that METH induced more deleterious effects in the myocardial tissues during acute and chronic administrations when under stress conditions. Heat shock proteins (Hsps) played a critical role in the acute phase, while numerous genes, including anti‑oxidant, anti‑apoptotic and physiological function genes, played significant roles in the chronic phase. These results indicate that METH abuse, ranging from episodes of binge abuse to chronic abuse over several years, may cause severe myocardial damage in human users under stress.
authors.affiliation: Department of Medical Toxicology, Kawasaki Medical School, Kurashiki 701‑0192, Japan. toxicology@med.kawasaki-m.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tomita
authors.forename: Toshiko
authors.initials: T
authors.lastname: Okuyama
authors.forename: Hironobu
authors.initials: H
authors.lastname: Katsuyama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Kotaro
authors.initials: K
authors.lastname: Shinone
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nata
authors.forename: Takaki
authors.initials: T
authors.lastname: Ishikawa
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012149:Restraint, Physical; D013312:Stress, Physiological; D013696:Temperature; D013997:Time Factors
chemical_list: D018663:Adrenergic Agents; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D008694:Methamphetamine; D003345:Corticosterone