Role of spinal metabotropic glutamate receptor subtype 5 in the development of tolerance to morphine-induced antinociception in rat |
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| Authors: | Tao Xu Wei Jiang Dongping Du Yongming Xu Qian Hu Qin Shen |
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| Affiliation: | 1. Department of Anesthesiology, Shanghai Sixth People''s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China;2. Pain Clinic Center, Shanghai Sixth People''s Hospital Affiliated to Shanghai Jiaotong University, China;3. School of Medicine of Shanghai Jiaotong University, China |
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| Abstract: | 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 Ca2+ 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. |
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| Keywords: | i.t., intrathecal mGluR5, metabotropic glutamate receptor subtype5 NMDA, N-methyl d-aspartate MPEP, methyl-6-(phenylethynyl)-pyridine hydrochloride CHPG, 2-chloro-5-hydroxyphenylglycine i.c.v., intracerebroventricular PKC, protein kinase C PLC, phospholipase C PI, phosphatidylinositol DAG, diacylglycerol IP3, inositol (1,4,5)-triphosphate CSF, cerebrospinal fluid SCI, spinal cord injury |
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