A SINGLE HIGH DOSE OF METHAMPHETAMINE INDUCES APOPTOTIC AND NECROTIC STRIATAL CELL LOSS LASTING UP TO 3 MONTHS IN MICE

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 striate! 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 striatel 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 striatel 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. Striatel 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. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.