title: A single high dose of methamphetamine induces apoptotic and necrotic striatal cell loss lasting up to 3 months in mice.
abstract: Methamphetamine (METH) is an addictive agent that poses a public health problem due to its toxic effects on neural tissue. We have shown that METH induces striatal lesions (cell loss) within 24 h of administration. Because cell proliferation has been found to follow excitotoxic and other types of lesions in adult brain, we tested the hypothesis that cell proliferation would follow METH-induced striatal cell death. To that end, METH (30 mg/kg i.p.) was injected into adult male mice followed by a single injection of the proliferation marker 5-bromo-2'-deoxyuridine (BrdU, 100 mg/kg i.p.) at various times post-METH up to 12 weeks. Immunohistochemical analysis of striatal tissue showed that METH-treated animals incorporated BrdU between 24-48 h post-METH. To determine the survival of the newly generated cells, a subgroup of animals received BrdU 36 h after METH and were sacrificed at various times up to 12 weeks post-METH. Morphological analysis of striatal tissue from these animals showed that by 12 weeks post-METH, approximately 42% and 30% of the newly generated cells showed pyknotic or necrotic morphology, respectively. Thus, approximately 30% of the newly generated cells survive up to 12 weeks post-METH. Striatal volume was increased by METH and normalized to control levels by 12 weeks after METH. The data demonstrate that a single bolus injection of METH induces cellular changes and responses that persist for months after exposure to METH.
authors.affiliation: Department of Biological Sciences, Hunter College of the City University of New York, New York, NY, USA.
authors.forename: I
authors.initials: I
authors.lastname: Tulloch
authors.forename: L
authors.initials: L
authors.lastname: Afanador
authors.forename: I
authors.initials: I
authors.lastname: Mexhitaj
authors.forename: N
authors.initials: N
authors.lastname: Ghazaryan
authors.forename: A G
authors.initials: AG
authors.lastname: Garzagongora
authors.forename: J A
authors.initials: JA
authors.lastname: Angulo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D002552:Cerebral Ventricles / Q000166:cytology / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009336:Necrosis / Q000139:chemically induced; D013995:Time; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D014404:Tubulin; D008694:Methamphetamine; D001973:Bromodeoxyuridine