Naloxone blocks anxiolytic-like effects of benzodiazepines in Swiss but not in Balb/c mice.

The ability of naloxone to block the effects of the benzodiazepines chlordiazepoxide and diazepam was evaluated in Swiss and Balb/c mice subjected to the light/dark choice test of anxiety or to a choice paradigm for measuring spontaneous exploratory behaviour. In Swiss mice, naloxone (5 or 10 mg/kg) completely or partially suppressed the anxiolytic-like effects of chlordiazepoxide (5 mg/kg) and diazepam (1 mg/kg) in the light/dark test. Naloxone alone was ineffective. None of these compounds affected locomotion in the free exploratory test. In Balb/c mice, naloxone did not reduce the anxiolytic-like action of benzodiazepines in the light/dark test. Moreover, naloxone did not antagonize the decrease in neophobia observed after anxiolytic treatment in Balb/c mice in the free exploratory paradigm. In this strain, benzodiazepines produced an increase of locomotor activity, whereas naloxone decreased it. The stimulant effects of benzodiazepines on locomotor activity were abolished by naloxone. As naloxone (2 mg/kg) reversed the morphine-induced hyperthermia both in Swiss and in Balb/c mice, differences in possible pharmacokinetic factors between the two strains can be ruled out as an explanation for the failure of naloxone to antagonize anxiolytic-like effects in Balb/c mice. Therefore, the ability of naloxone to reverse anxiolytic effects does not hold for all strains of mice.