Anxiolytic activity of SC-48274 compared with those of buspirone and diazepam in experimental anxiety models

The present study was performed to assess the anxiolytic activity of the novel anxiolytic SC-48274 in comparison with those of buspirone and diazepam. Drugs were administered p.o. The experimental anxiety models included gastric lesions of mice induced by socio-psychological stress in the communication box (CB) and the passive avoidance paradigm in rats. In the CB experiments, non-foot-shocked mice (responder) exposed to the emotional responses of foot-shocked mice (sender), 3 hr per day for 3 days, developed gastric lesions. Single treatments of diazepam (1, 2, 5 mg/kg) and SC-48274 (25, 50 mg/kg) prevented gastric lesion formation, but buspirone at 2.5-10 mg/kg did not. A 3-day treatment with SC-48274 at doses over 5 mg/kg prevented gastric lesions; and a 3-day treatment with buspirone at 2, 5 and 10 mg/kg prevented the lesions with a U-shaped dose-response. Diazepam also prevented gastric lesion formation at the doses of 1 and 2 mg/kg. In the passive avoidance response study, rats which had a single acquisition trial for 2 days were used. The step-down latency for rats to enter from the illuminated compartment to the dark one was recorded. Single treatments of SC-48274 (25 mg/kg), diazepam (5, 10 mg/kg) or buspirone (25 mg/kg) shortened the delayed latency. These results suggest that SC-48274 has anxiolytic activity of the same potency as buspirone and repeated-dose administration is needed to induce anxiolytic activity.