title: Mu-opioid receptor knockout mice are more sensitive to chlordiazepoxide-induced anxiolytic behavior.
abstract: We have previously demonstrated benzodiazepine binding in the cortex and hippocampus of mu-opioid receptor knockout (KO) mice. It is known that benzodiazepine receptors are involved in regulating anxiety-like behaviors. Thus, the present study was designed to examine whether there are changes in anxiety-like behavior in mice lacking mu-opioid receptors. To produce anxiolytic activity (less anxiety), the prototype benzodiazepine receptor agonist chlordiazepoxide (CDP, 5 mg/kg) was intraperitoneally administered in wild type (WT) and mu-opioid receptor KO mice. We found that compared to WT mice, mu-opioid receptor KO mice showed enhanced anxiolytic activity to CDP, including increased number of entries into open arm, increased percentage of the time spent in open arms, and decreased percentage of the time spent in enclosed arms in the elevated plus-maze test. We also assessed protein expression of the gamma-aminobutyric acid (GABA) synthetic enzyme (glutamic acid decarboxylase; GAD). Western blotting data indicated that neither the lack of mu-opioid receptors nor CDP treatment altered cortical or hippocampal GAD₆₅ or GAD₆₇ protein expression. These data indicate that compared with WT, mu-opioid receptor KO mice experienced less anxiety and exhibited enhanced anxiolytic activity to CDP treatment, and these effects were not dependent on GAD₆₅ or GAD₆₇ protein expression. Our previous and present data suggest that the anxiolytic activity displayed in mu-opioid receptor KO mice is associated with upregulation of the benzodiazepine receptor system.
authors.affiliation: Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan, ROC.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Wang
authors.forename: Yih-Jing
authors.initials: YJ
authors.lastname: Lee
authors.forename: Lir-Wan
authors.initials: LW
authors.lastname: Fan
authors.forename: Pao-Pao
authors.initials: PP
authors.lastname: Yang
authors.forename: Pao-Luh
authors.initials: PL
authors.lastname: Tao
authors.forename: Ing-Kang
authors.initials: IK
authors.lastname: Ho
authors.forename: Lu-Tai
authors.initials: LT
authors.lastname: Tien
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002707:Chlordiazepoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000172:deficiency*; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D017450:Receptors, Opioid, mu; D002707:Chlordiazepoxide; D005968:Glutamate Decarboxylase