Document Detail

Selective vulnerability in striosomes and in the nigrostriatal dopaminergic pathway after methamphetamine administration : early loss of TH in striosomes after methamphetamine.
MedLine Citation:
PMID:  19760475     Owner:  NLM     Status:  MEDLINE    
Methamphetamine (METH), a commonly abused psychostimulant, causes dopamine neurotoxicity in humans, rodents, and nonhuman primates. This study examined the selective neuroanatomical pattern of dopaminergic neurotoxicity induced by METH in the mouse striatum. We examined the effect of METH on tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoreactivity in the different compartments of the striatum and in the nucleus accumbens. The levels of dopamine and its metabolites, 3,4-dihidroxyphenylacetic acid and homovanillic acid, as well as serotonin (5-HT) and its metabolite, 5-hydroxyindolacetic acid, were also quantified in the striatum. Mice were given three injections of METH (4 mg/kg, i.p.) at 3 h intervals and sacrificed 7 days later. This repeated METH injection induced a hyperthermic response and a decrease in striatal concentrations of dopamine and its metabolites without affecting 5-HT concentrations. In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals. Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix. The predominant loss of dopaminergic terminals in the striosomes occurred along the rostrocaudal axis of the striatum. In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens. These results provide the first evidence that compartments of the mouse striatum, striosomes and matrix, and mesolimbic and nigrostriatal pathways have different vulnerability to METH. This pattern is similar to that observed with other neurotoxins such as MPTP, the most widely used model of Parkinson's disease, in early Huntington's disease and hypoxic/ischemic injury, suggesting that these conditions might share mechanisms of neurotoxicity.
Noelia Granado; Sara Ares-Santos; Esther O'Shea; Carlos Vicario-Abejón; M Isabel Colado; Rosario Moratalla
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-04
Journal Detail:
Title:  Neurotoxicity research     Volume:  18     ISSN:  1476-3524     ISO Abbreviation:  Neurotox Res     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-05-25     Completed Date:  2010-08-31     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  100929017     Medline TA:  Neurotox Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  48-58     Citation Subset:  IM    
Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avda. Dr. Arce 37, 28002, Madrid, Spain.
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MeSH Terms
Corpus Striatum / drug effects*,  metabolism
Dopamine / metabolism*
Dopamine Agents / toxicity*
Dopamine Plasma Membrane Transport Proteins / metabolism
Drug Administration Schedule
Gene Expression Regulation / drug effects
Homovanillic Acid / metabolism
Methamphetamine / toxicity*
Mice, Inbred C57BL
Neural Pathways / drug effects,  metabolism
Nucleus Accumbens / drug effects,  metabolism
Substantia Nigra / drug effects*,  metabolism
Tyrosine 3-Monooxygenase / metabolism*
Reg. No./Substance:
0/Dopamine Agents; 0/Dopamine Plasma Membrane Transport Proteins; 306-08-1/Homovanillic Acid; 537-46-2/Methamphetamine; EC 3-Monooxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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