Role of spinal metabotropic glutamate receptor subtype 5 in the development of tolerance to morphine-induced antinociception in rat.
Prolonged intrathecal (i.t.) administration of morphine results in tolerance to morphine-induced antinociception. We found that co-administration of selective metabotropic glutamate receptor subtype 5 antagonist MPEP with morphine could suppress the loss of morphine-induced antinociception and inhibit the development of tolerance to morphine-induced antinociceptive effect. Whereas, the specific metabotropic glutamate receptor subtype 5 agonist CHPG does the opposite. As the activation of NMDA receptor after chronic morphine administration has been verified, we suppose there is an enhanced activation of mGluR5 during the development of tolerance to morphine-induced antinociception. Activation of mGluR5 may mobilize the release of intracellular Ca(2+) and activate PKC, leading to morphine-induced antinociception suppression. We conclude that mGluR5 contributes to the development of tolerance to morphine-induced antinociception after chronic morphine exposure.
Xu
Tao
T
Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China.
Jiang
Wei
W
Du
Dongping
D
Xu
Yongming
Y
Hu
Qian
Q
Shen
Qin
Q
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010648:Phenylacetates / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C107349:2-chloro-5-hydroxyphenylglycine; D000701:Analgesics, Opioid; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D010648:Phenylacetates; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D009020:Morphine; C121465:6-methyl-2-(phenylethynyl)pyridine; D011493:Protein Kinase C; D002118:Calcium; D005998:Glycine