Anxiolytic profile of GR 38032F in the potentiated startle paradigm.

The potentiated startle paradigm has been demonstrated to be a model of anxiety sensitive to a range of established and putative anxiolytics. This study reports a preliminary investigation of the effects of the 5-HT(3) antagonist GR 38032F on potentiated startle. Doses of 0.01 and 0.1mg/kg each showed an anxiolytic profile in significantly reducing startle amplitude, with the lower dose having an effect comparable to chlordiazepoxide at 5.0mg/kg. 5-hydroxytryptophan at 25mg/kg significantly enhanced startle amplitude, and a mutual antagonism was found when 5-HTP was combined with GR 38032F. The results extend previous work with other models of anxiety suggesting anxiolytic potential for GR 38032F, and further demonstrate the possibility that the anxiolytic effect is mediated by serotonergic mechanisms.