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 a nxiety, including the elevated plus-maze. Although naloxone preferenti ally binds to the mu opioid receptor, its selectivity is rather low. T he opioid receptor subtype important for anxiolytic-like actions of be nzodiazepines in the plus-maze remains, therefore, unknown. In the pre sent experiments, the ability of antagonists selective for subtypes of the opioid receptor to block the anxiolytic-like effects of chlordiaz epoxide in the elevated plus-maze was evaluated in Swiss mice. Chlordi azepoxide, 5 mg/kg, increased the proportion as well as the number of open arms entries without modifying closed arms entries. Lower doses o f 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-funaltrexamin e, 10 mg/kg, reduced the effects of the benzodiazepine while the dose of 20 mg/kg completely blocked the effects. Nor-binaltorphimine was in effective at a dose of 2.5 mg/kg, but completely inhibited the actions of chlordiazepoxide when the dose was 5 mg/kg. Naltrindole was ineffe ctive. None of the antagonists affected plus-maze behavior when admini stered alone. It was concluded that the mu and kappa receptors are imp ortant for the anxiolytic-like actions of chlordiazepoxide in the elev ated plus maze. (C) 1998 Elsevier Science Ltd. All rights reserved.