title: Effects of aquaporin 4 deficiency on morphine analgesia and chronic tolerance: a study at spinal level.
abstract: Recent reports showed that aquaporin 4 (AQP4) deficiency potentiated morphine analgesia but attenuated chronic morphine-induced tolerance in hot-plate test, predominantly reflecting supraspinal pain response. The present study investigated the effects of AQP4 deficiency on morphine analgesia and tolerance using tail flick test, primarily reflecting spinal response. It was found that (1) chronic morphine treatment resulted in decreased expression of spinal AQP4 in mice detected by Western blotting analysis; (2) in tail flick test, AQP4 knockout mice displayed significant impaired morphine analgesia without influencing the progress of chronic tolerance; and (3) the expressions of mu-opioid receptor (MuOR) and glutamate transporter 1 (GLT-1) in AQP4 knockout mice spinal cord were lower than those in wild-type mice, whereas chronic morphine-induced alteration characteristics of spinal MuOR or GLT-1 expression were not affected by AQP4 deficiency. In conclusion, AQP4 deficiency attenuated morphine acute antinociception but did not affect chronic tolerance in tail flick test, implying a role for spinal AQP4 in morphine analgesia but not in chronic tolerance.
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Meng-Ling
authors.initials: ML
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Bao
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Zhao
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D051401:Aquaporin 4 / Q000172:deficiency* / Q000235:genetics; D001253:Astrocytes / Q000502:physiology; D002908:Chronic Disease; D004361:Drug Tolerance / Q000502:physiology*; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000235:genetics*; D010147:Pain Measurement / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D027342:Excitatory Amino Acid Transporter 2; D017450:Receptors, Opioid, mu; D009020:Morphine
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