Naloxone potentiates the anxiolytic but not the amnestic action of chlordiazepoxide in C57BL/6 mice.

This study aimed to investigate the effects of the opiate antagonist naloxone (10 mg/kg) on the action of a subeffective dose of chlordiazepoxide. C57BL/6 mice were tested for either anxiety, using an elevated plus maze, emotional memory in a passive avoidance paradigm or spatial memory in a radial maze. In the elevated plus maze, chlordiazepoxide 2.5 mg/kg was ineffective per se but, when combined with naloxone, it increased the proportion of open-arm entries, as did a higher dose of chlordiazepoxide (5 mg/kg). Closed-arm entries were increased with chlordiazepoxide (2.5 mg/kg) injected alone but naloxone, alone or combined with chlordiazepoxide, did not modify this measure. In the passive avoidance test, chlordiazepoxide 2.5 mg/kg decreased the latency to enter a compartment associated with an electric foot-shock, while a dose of 1.25 mg/kg, alone or in combination with naloxone, was ineffective. Finally, in the radial arm maze, chlordiazepoxide (5 mg/kg) induced amnesia. However, a dose of 2.5 mg/kg, alone or with naloxone, had no effect on learning. Naloxone elicited no intrinsic action in any of these behavioural models. It can be concluded that naloxone potentiates the anxiolytic but not the amnestic action of chlordiazepoxide.