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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-11-15
pubmed:abstractText
There are several lines of evidence implying the involvement of the central glutamatergic system in morphine dependence. Extracellular glutamate released from nerve terminals is counterbalanced by glutamate transporters in neurons (EAAC1 and EAAT4) and glial cells (GLT-1 and GLAST), thereby modulating the glutamatergic system and protecting neurons from an excitotoxic action of glutamate. Here we show that a glial glutamate transporter GLT-1 could be involved in physical and psychological morphine dependence. By Northern blot analysis, the expression of glial glutamate transporter GLT-1, but not GLAST, mRNA was decreased in the striatum/nucleus accumbens (NAc) and thalamus of morphine-dependent rats. Subcutaneous administration of a glutamate transporter activator suppressed the development of physical morphine dependence and morphine-induced conditioned place preference. Intracerebroventricular administration of a glutamate transporter inhibitor to morphine-dependent rats facilitated the expression of naloxone-precipitated morphine withdrawal-induced somatic signs and conditioned place aversion. Furthermore, gene transfer techniques using recombinant adenoviruses revealed that GLT-1 in the locus coeruleus and NAc shell plays inhibitory roles in physical and psychological morphine dependence, respectively. These findings may provide evidence that a glial glutamate transporter GLT-1 could be a new target for preventing physical and psychological morphine dependence.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
1025
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
383-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Involvement of glial glutamate transporters in morphine dependence.
pubmed:affiliation
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. msatoh@pharm.kyoto-u.ac.jp
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't