Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra cell loss

被引:94
作者
Harvey, DC
Lacan, G
Tanious, SP
Melega, WP
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA
关键词
methamphetamine; neurotoxicity; neurodegeneration; PET; neuronal plasticity; Parkinson's disease;
D O I
10.1016/S0006-8993(00)02439-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
After administration of methamphetamine (METH) (2x2: mg/kg, 6 h apart) to vervet monkeys, long term but reversible dopaminergic deficits were observed in both in vivo and post-mortem studies. Longitudinal studies using positron emission tomography (PET) with the dopamine transporter (DAT)-binding ligand, [C-11]WIN 35,428 (WIN), were used to show decreases in striatal WIN binding of 80% at 1 week and only 10% at 1.5 years. A post-mortem characterization of other METH subjects at 1 month showed extensive decreases in immunoreactivity (IR) profiles of tyrosine hydroxylase (TH), DAT and vesicular monoamine transporter-2 (VMAT) in the striatum, medial forebrain bundle and the ventral midbrain dopamine (VMD) cell region. These IR deficits were not associated with a loss of VMD cell number when assessed at 1.5 years by stereological methods. Further, at 1.5],ears, IR profiles of METH subjects throughout the nigrostriatal dopamine system appeared similar to controls although some regional deficits persisted. Collectively, the magnitude and extent of the dopaminergic deficits, and the subsequent recovery were not suggestive of extensive axonal degeneration followed by regeneration. Alternatively, this apparent reversibility of the METH-induced neuroadaptations may be related primarily to long-term decreases in expression of VMD-related proteins that recover over time. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:259 / 270
页数:12
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