Lack of effects of 5HT3 receptor antagonists in the social interaction and elevated plus-maze tests of anxiety in the rat.

The effects of three 5HT3 receptor antagonists: BRL 43964 (0.1 and 1 mg/kg, oral), GR 38032F (0.1 and 1 mg/kg, oral), and zacopride (0.01, 0.1 and 1 mg/kg, IP) were examined in low light test conditions of the social interaction test. None of the three 5HT3 receptor antagonists had a significant effect on social interaction. In contrast, in two experiments chlordiazepoxide (7.5 mg/kg) significantly increased social interaction and this effect was greatest in the unfamiliar test condition. In a third experiment, the effects of GR 38032F (0.1 and 1 mg/kg, oral) and zacopride (0.01, 0.1 and 1 mg/kg, oral) were investigated in the high light test conditions of the social interaction test; neither compound had a significant effect. In the elevated plus-maze, chlordiazepoxide (7.5 mg/kg oral or IP) significantly increased both the per cent number of entries made onto open arms and the per cent of time spent on the open arms, indicating an anxiolytic action. Zacopride (0.01, 0.1 and 1 mg/kg, oral or IP) had no significant effect in this test. The effect of the baseline rate of responding in the social interaction test on the effects of 5-HT3 antagonists is discussed. The results from the present experiment and those from other animal tests of anxiety caution against the conclusion that 5HT3 receptor antagonists are anxiolytic.