title: Con-T[M8Q] potently attenuates the expression and development of morphine tolerance in mice.
abstract: As a variant of peptide conantokin-T (con-T), con-T[M8Q] is derived from the venom of Conus tulipa. Our previous study has demonstrated that con-T[M8Q] selectively targets N-methyl-d-aspartate receptor (NMDAR) NR2B subunit. In the present study, we determined the effects of con-T[M8Q] on the expression and development of morphine tolerance using hot plate test and acetic acid writhing test. Our results demonstrated that con-T[M8Q] could efficiently attenuate the expression and development of morphine analgesic tolerance in mice at low doses (5-20nmol/kg), and it exhibited more potent effects compared with ifenprodil, a typical small-molecule antagonist of NMDAR. In addition, low doses of con-T[M8Q] (5-20nmol/kg) did not cause drug resistance and apparent analgesic activity compared with morphine. Taken together, con-T[M8Q] could be a promising new candidate in attenuating morphine tolerance.
authors.affiliation: College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, PR China; Beijing Institute of Biotechnology, Beijing 100071, PR China.
authors.forename: Baolan
authors.initials: B
authors.lastname: Ren
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, PR China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, PR China.
authors.forename: Zhuguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, PR China.
authors.forename: Bailin
authors.initials: B
authors.lastname: Li
authors.affiliation: College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ou
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, PR China. Electronic address: qy_dai@yahoo.com.
authors.forename: Qiuyun
authors.initials: Q
authors.lastname: Dai
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D020916:Conotoxins; D004361:Drug Tolerance; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008978:Mollusk Venoms / Q000494:pharmacology*; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000523:psychology
chemical_list: D000701:Analgesics, Opioid; D020916:Conotoxins; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms; C121001:NR2B NMDA receptor; D009292:Narcotic Antagonists; D010455:Peptides; D016194:Receptors, N-Methyl-D-Aspartate; C063571:conantokin-T; D009270:Naloxone; D009020:Morphine
keywords: Con-T[M8Q]; Conantokins; Morphine; NMDAR; Tolerance