Blockade of anxiolytic-like actions of chlordiazepoxide by naloxone in the elevated plus-maze: Comparisons between Swiss, C57BL/6, and BALB/c mice

Abstract

The ability of the opiate antagonist naloxone to block the anxiolytic- like effects of chlordiazepoxide in the elevated plus-maze was evaluated in Swiss, C57BL/6, and BALB/c mice. In our version of this procedure, a dose of 5 mg/kg of chlordiazepoxide was necessary in all three strains to increase the proportion of open-arms entries, the parameter supposed to best represent anxiolytic activity. No significant effect was obtained on closed-arms entries, suggesting that the anxiolytic-like effect observed was not a consequence of locomotor stimulation. However, in the BALB/c mice, there was a nonsignificant tendency for an increase of closed-arms entries. When chlordiazepoxide, 5 mg/kg, was combined with naloxone, 10 mg/kg, the effects of the benzodiazepine were blocked in the Swiss and C57BL/6 strains but not in the BALB/c strain. If anything, naloxone seemed to enhance the actions of chlordiazepoxide in this strain, but this effect failed to reach statistical significance. The antagonism by naloxone of the anxiolytic-like effects of chlordiazepoxide in the Swiss and C57BL/6 strains coincides with previous results obtained in the rat and in the light/dark choice test and the free exploratory paradigm in mice. The lack of antagonism in the BALB/c strain also coincides with previous results from these procedures. It is suggested that the opioid system is not important for the anxiolytic-like actions of benzodiazepines in BALB/c mice. This may be due to no or small release of opioids in response to stress in this strain.