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 ofthis procedure, a dose of 5 mglkg of chlordiazepoxide was necessary in all three strains to increase the proportion of open-arms entries, the parameter supposed to best represent anxiolYtlc 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 mglkg, was combined with naloxone, 10 mglkg, 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.

µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice

“…For example, when coadministered with subeffective doses of benzodiazepines, i.e., positive allosteric modulators at the GABA receptor, naloxone (10 mg/kg intraperitoneally) potentiated their anxiolytic-like effect in the elevated plus maze [ 50 – 55 ]. Note, however, that others demonstrated an attenuation of the anxiolytic-like effects of benzodiazepines with naloxone in rodents [ 56 – 58 ]. Further, in the present study, CTAP, a selective μ−opioid receptor antagonist, administered intracerebroventricularly potentiated the anxiolytic-like effect of oxytocin, demonstrating that the anxiolytic-like effect of oxytocin is potentiated by blocking the central action of endogenous opioids at μ−opioid receptors.…”