The role of subtypes of the opioid receptor in the anxiolytic action of chlordiazepoxide.

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.