The role of subtypes of the opioid receptor in the anxiolytic action of chlordiazepoxide. Agmo, A. & Belzung, C. Neuropharmacology, 37(2):223--232, 1998.
abstract   bibtex   
Previous studies have shown that the opiate antagonist naloxone blocks the anxiolytic-like effects of benzodiazepines in several models of anxiety, including the elevated plus-maze. Although naloxone preferentially binds to the mu opioid receptor, its selectivity is rather low. The opioid receptor subtype important for anxiolytic-like actions of benzodiazepines in the plus-maze remains, therefore, unknown. In the present experiments, the ability of antagonists selective for subtypes of the opioid receptor to block the anxiolytic-like effects of chlordiazepoxide in the elevated plus-maze was evaluated in Swiss mice. Chlordiazepoxide, 5 mg/kg, increased the proportion as well as the number of open arms entries without modifying closed arms entries. Lower doses of the benzodiazepine were ineffective. The mu receptor antagonist beta-funaltrexamine, 10 and 20 mg/kg, the delta antagonist naltrindole, 10 mg/kg, and the kappa antagonist nor-binaltorphimine, 2.5 and 5 mg/kg, were then combined with chlordiazepoxide, 5 mg/kg. beta-funaltrexamine, 10 mg/kg, reduced the effects of the benzodiazepine while the dose of 20 mg/kg completely blocked the effects. Nor-binaltorphimine was ineffective at a dose of 2.5 mg/kg, but completely inhibited the actions of chlordiazepoxide when the dose was 5 mg/kg. Naltrindole was ineffective. None of the antagonists affected plus-maze behavior when administered alone. It was concluded that the mu and kappa receptors are important for the anxiolytic-like actions of chlordiazepoxide in the elevated plus maze.
@article{ agmo_role_1998,
  title = {The role of subtypes of the opioid receptor in the anxiolytic action of chlordiazepoxide},
  volume = {37},
  issn = {0028-3908},
  abstract = {Previous studies have shown that the opiate antagonist naloxone blocks the anxiolytic-like effects of benzodiazepines in several models of anxiety, including the elevated plus-maze. Although naloxone preferentially binds to the mu opioid receptor, its selectivity is rather low. The opioid receptor subtype important for anxiolytic-like actions of benzodiazepines in the plus-maze remains, therefore, unknown. In the present experiments, the ability of antagonists selective for subtypes of the opioid receptor to block the anxiolytic-like effects of chlordiazepoxide in the elevated plus-maze was evaluated in Swiss mice. Chlordiazepoxide, 5 mg/kg, increased the proportion as well as the number of open arms entries without modifying closed arms entries. Lower doses of the benzodiazepine were ineffective. The mu receptor antagonist beta-funaltrexamine, 10 and 20 mg/kg, the delta antagonist naltrindole, 10 mg/kg, and the kappa antagonist nor-binaltorphimine, 2.5 and 5 mg/kg, were then combined with chlordiazepoxide, 5 mg/kg. beta-funaltrexamine, 10 mg/kg, reduced the effects of the benzodiazepine while the dose of 20 mg/kg completely blocked the effects. Nor-binaltorphimine was ineffective at a dose of 2.5 mg/kg, but completely inhibited the actions of chlordiazepoxide when the dose was 5 mg/kg. Naltrindole was ineffective. None of the antagonists affected plus-maze behavior when administered alone. It was concluded that the mu and kappa receptors are important for the anxiolytic-like actions of chlordiazepoxide in the elevated plus maze.},
  language = {eng},
  number = {2},
  journal = {Neuropharmacology},
  author = {Agmo, A. and Belzung, C.},
  year = {1998},
  pmid = {9680247},
  keywords = {Animals, Anti-Anxiety Agents, Anxiety, Chlordiazepoxide, Male, Mice, Naltrexone, Narcotic Antagonists, Receptors, Opioid},
  pages = {223--232}
}
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