Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-8-22
pubmed:abstractText
It is well known that prolonged exposure to morphine results in tolerance to morphine-induced antinociception. In the present study, we found that either intrathecal (i.t.) or subcutaneous (s.c.) injection of the selective metabotropic glutamate receptor 5 (mGluR5) antagonist, methyl-6-(phenylethynyl)-pyridine hydrochloride (MPEP), attenuated the development of tolerance to morphine-induced antinociception. Using the receptor binding assay, we found here that the number of mGluR5 in the mouse spinal cord was significantly increased by repeated treatment with morphine. Furthermore, repeated treatment with morphine produced a significant increase in the level of mGluR5 immunoreactivity in the dorsal horn of the mouse spinal cord. Double-labeling experiments showed that the increased mGluR5 was predominantly expressed in the neurons and sparsely expressed in the processes of astrocytes following repeated treatment with morphine. Consistent with these results, the response of Ca2+ to the selective group I mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG), in cultured spinal cord neurons was potently enhanced by 3 days of in vitro treatment with morphine. These findings support the idea that the increased mGluR5 following repeated treatment with morphine leads to enhanced neuronal excitability and synaptic transmission in the dorsal horn of the spinal cord and, in turn, suppresses the morphine-induced antinociception in mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1297-305
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16000152-Analgesics, Opioid, pubmed-meshheading:16000152-Animals, pubmed-meshheading:16000152-Calcium, pubmed-meshheading:16000152-Coculture Techniques, pubmed-meshheading:16000152-Drug Tolerance, pubmed-meshheading:16000152-Excitatory Amino Acid Antagonists, pubmed-meshheading:16000152-Intracellular Membranes, pubmed-meshheading:16000152-Male, pubmed-meshheading:16000152-Methoxyhydroxyphenylglycol, pubmed-meshheading:16000152-Mice, pubmed-meshheading:16000152-Mice, Inbred ICR, pubmed-meshheading:16000152-Morphine, pubmed-meshheading:16000152-Neuroglia, pubmed-meshheading:16000152-Neurons, pubmed-meshheading:16000152-Nociceptors, pubmed-meshheading:16000152-Osmolar Concentration, pubmed-meshheading:16000152-Pyridines, pubmed-meshheading:16000152-Receptors, Metabotropic Glutamate, pubmed-meshheading:16000152-Spinal Cord
pubmed:year
2005
pubmed:articleTitle
Involvement of spinal metabotropic glutamate receptor 5 in the development of tolerance to morphine-induced antinociception.
pubmed:affiliation
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Shinagawa-ku, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't