Effects of acute administration of the 5-HT3 receptor antagonist, BRL 46470A, on the behaviour of mice in a two compartment light-dark box and during social interactions in their home cage and an unfamiliar neutral cage.

Adult male CD1 mice received the 5-HT3 receptor antagonist, BRL 46470A, by intraperitoneal injection at three dose levels (2.5 mg/kg, 25 and 2.5 micrograms/kg). Controls were injected with physiological saline. At 30 min after injection, the behaviour of each mouse was examined by ethological procedures, when encountering an untreated partner for 5 min in its home cage and for 5 min in the more aversive situation of an unfamiliar neutral cage. The behaviour of each mouse also was monitored for 5 min in a two compartment light-dark box. At all doses tested, BRL 46470A increased the time spent in the light compartment of the light-dark box. At the smallest dose (2.5 micrograms/kg), the number of transitions between light and dark compartments was increased and there also was an increase (per unit time) in the numbers of squares crossed and number of scans in the light compartment. At all doses tested, BRL 46470A increased social investigation and reduced non-social exploratory activity in both the home cage and the unfamiliar neutral cage. In both test situations, increase of social investigation was maximum at 25 micrograms/kg, and at this dose, aggressive behaviour was also enhanced. In the neutral cage, digging in the sawdust by drug-treated mice showed a progressive dose-related increase. These results indicate potent anxiolytic-like activity by BRL 46470A and also demonstrate increased reactivity to unfamiliar environmental stimuli, such as novel sawdust. The significance of these findings is discussed.