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Involvement of spinal metabotropic glutamate receptor 5 in the development of tolerance to morphine‐induced antinociception
Author(s) -
Narita Minoru,
Suzuki Masami,
Narita Michiko,
Niikura Keiichi,
Nakamura Atsushi,
Miyatake Mayumi,
Aoki Takeshi,
Yajima Yoshinori,
Suzuki Tsutomu
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03296.x
Subject(s) - metabotropic glutamate receptor 5 , morphine , metabotropic glutamate receptor , metabotropic receptor , pharmacology , agonist , spinal cord , glutamate receptor , chemistry , metabotropic glutamate receptor 1 , medicine , receptor , neuroscience , biology
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 Ca 2+ 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.