Document Detail

Protective effects of MK-801 on methamphetamine-induced depletion of dopaminergic and serotonergic terminals and striatal astrocytic response: an immunohistochemical study.
MedLine Citation:
PMID:  7725247     Owner:  NLM     Status:  MEDLINE    
It has been shown previously that methamphetamine induces dopaminergic nerve terminal degeneration, serotonin depletion and striatal reactive astrogliosis, and that the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 can block methamphetamine (MA)-induced depletion of dopamine and serotonin and reduction in activity of their synthetic enzymes. In this study, immunohistochemistry was used to evaluate the effect of MK-801 on methamphetamine-induced neuropathological alterations of dopaminergic and serotonergic terminals and striatal astrocytic responses. Adult male rats were treated with methamphetamine (4 injections of 10 mg/kg at 2 hour intervals) in conjunction with MK-801 which was administered 15 min before each methamphetamine administration at doses of 1 mg/kg or 2 mg/kg. Brains were examined three days following treatment. MK-801 administration prevented methamphetamine-induced depletion of 5-hydroxytryptophan (5-HT) terminals in the forebrain and depletion of tyrosine hydroxylase-positive dopaminergic terminals and astrocytic response in the neostriatum in most animals. These results support the concept that excitatory amino acids acting through an NMDA receptor are involved in methamphetamine-induced neuronal damage on dopaminergic and serotonergic terminal fields. A minor depletion of TH-positive terminals and astrogliosis in the neostriatum was seen in three of nine MA-MK-801-treated animals. This indicates that the protective effects of MK-801 on MA-induced dopaminergic terminal degeneration varies among animals with complete protection in most animals and partial protection in the others using the present doses and dosing regimen.
C Pu; C V Vorhees
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  19     ISSN:  0887-4476     ISO Abbreviation:  Synapse     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-05-25     Completed Date:  1995-05-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  97-104     Citation Subset:  IM    
Division of Basic Science Research, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
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MeSH Terms
Corpus Striatum
Dizocilpine Maleate / pharmacology*
Dopamine / pharmacology
Neurons / pathology*
Rats, Sprague-Dawley
Serotonin / pharmacology
Grant Support
Reg. No./Substance:
50-67-9/Serotonin; 537-46-2/Methamphetamine; 77086-22-7/Dizocilpine Maleate

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

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