Anxiolytic effects of buspirone and gepirone in the fear-potentiated startle paradigm.

Fear potentiation of the acoustic startle reflex was produced by eliciting startle responses in the presence of a light that had been previously paired with a shock. Buspirone (0.6-5.0 mg/kg) and gepirone (1.25-10.0 mg/kg), but not their common metabolite, 1-PP (0.5-40 mg/kg), produced a dose-dependent reduction of fear-potentiated startle. These doses of buspirone and gepirone slightly increased baseline startle levels. Reduction of fear-potentiated startle appears to involve supraspinal sites of action, since intraventricular but not intrathecal administration of buspirone (200 micrograms) reduced fear-enhanced startle. Both buspirone and gepirone were highly efficacious in this model compared to other animal tests that are used to study anxiolytic compounds.