Document Detail

Reduced degeneration of dopaminergic terminals and accentuated astrocyte activation by high dose methamphetamine administration in nociceptin receptor knock out mice.
MedLine Citation:
PMID:  20025929     Owner:  NLM     Status:  MEDLINE    
A major pathology of methamphetamine abuse is loss of dopaminergic function due to destruction of dopaminergic terminals, especially in the striatum. This process is accompanied by gliosis by astrocytes and microglia. Here, we evaluated the function of endogenous nociceptin/orphanin FQ in these events using nociceptin receptor (NOP) knockout mice. Wild-type and knockout mice were injected systemically either saline vehicle or 5mg/kg methamphetamine four times interspersed by 2h intervals. Three days later, brains were immunohistochemically processed to visualize methamphetamine-induced loss of tyrosine hydroxylase (as a marker of damage to dopamine terminals), glial fibrillary acidic protein (GFAP, as a marker of astrocytes), and ionized calcium-binding adapter molecule 1 (lba-1, as a marker of microglia) in the striatum. Methamphetamine treatment induced an approximately 80% loss of tyrosine hydroxylase-immunoreactivity, and this effect was mildly attenuated in NOP receptor knockout mice. There was a large increase (approximately 15-fold) in GFAP-immunoreactivity in methamphetamine-treated wild-type mice, which was almost two times larger still in NOP receptor knockout mice. In contrast, Iba-1 immunostaining was only modestly increased (approximately 30%) by methamphetamine treatment, and there were no difference between genotypes. Finally, there were no genotype-dependent differences in hyperthermic responses to methamphetamine. These results indicate that endogenous nociceptin/orphanin FQ exacerbates the neurotoxic effects of methamphetamine on striatal dopamine neurons, and suggests this is due in part to an astrocyte-mediated event.
Kazuto Sakoori; Niall P Murphy
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Publication Detail:
Type:  Journal Article     Date:  2009-12-16
Journal Detail:
Title:  Neuroscience letters     Volume:  469     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-04-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  309-13     Citation Subset:  IM    
Copyright Information:
(c) 2009 Elsevier Ireland Ltd. All rights reserved.
Molecular Neuropathology Group, RIKEN Brain Science Institute, 2-1 Hirosawa, Wakoshi, Saitama, 351-0198, Japan.
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MeSH Terms
Astrocytes / drug effects*,  physiology
Calcium-Binding Proteins / metabolism
Central Nervous System Stimulants / administration & dosage,  pharmacology*
Corpus Striatum / drug effects,  physiopathology
Dopamine / metabolism*
Fever / chemically induced,  physiopathology
Glial Fibrillary Acidic Protein / metabolism
Methamphetamine / administration & dosage,  pharmacology*
Mice, Knockout
Microglia / drug effects,  physiology
Nerve Degeneration / drug therapy*,  physiopathology
Neurons / drug effects,  physiology
Receptors, Opioid / genetics,  metabolism*
Tyrosine 3-Monooxygenase / metabolism
Reg. No./Substance:
0/Aif1 protein, mouse; 0/Calcium-Binding Proteins; 0/Central Nervous System Stimulants; 0/Glial Fibrillary Acidic Protein; 0/Receptors, Opioid; 0/nociceptin receptor; 537-46-2/Methamphetamine; EC 3-Monooxygenase

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

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