The anxiogenic action of RO 5-4864 in the social interaction test: effect of chlordiazepoxide, RO 15-1788 and CGS 8216

Abstract

RO 5-4864 (20 mg/kg), a benzodiazepine with high affinity for peripheral-type benzodiazepine binding sites in rat kidney and brain, but not for the "classical" CNS sites, reduced the time spent by pairs of rats in active social interaction, without reducing locomotor activity, possibly reflecting an anxiogenic action. This anxiogenic effect was not reversed by chlordiazepoxide (5 or 10 mg/kg) given acutely, but was reversed by chlordiazepoxide (5 mg/kg) given for 5 days prior to testing. RO 15-1788 (10 mg/kg), a drug that antagonises several effects of benzodiazepines but has little affinity for peripheral-type sites, had no action on the reduction in social interaction induced by RO 5-4864. However, CGS 8216 (10 mg/kg) which also antagonises the effects of benzodiazepines and has little affinity for RO 5-4864 recognition sites, significantly enhanced the reduction in social interaction caused by RO 5-4864, and the combination produced a significant decrease in locomotor activity. These results are discussed in terms of possible sites of action of RO 5-4864 on the GABA-benzodiazepine receptor complex.