Fear-potentiated startle and light-enhanced startle models in drug discovery

Described in this unit are the fear-potentiated startle (FPS) and light-enhanced startle (LES) tests. These protocols have proven reliable in detecting the anxiolytic properties of test compounds. The principle of these tests is that the magnitude of the acoustic startle reflex is an index of anxiety. The FPS test includes two training sessions in which an intrinsically aversive foot shock is paired with a neutral cue light. In the test session presentation of this cue light is subsequently used to elicit startle potentiation. In the LES test startle reactivity is increased by presentation of bright light. Because LES is based on the innate aversion of rodents for bright light it does not require training sessions. Although LES has been used less frequently than FPS for screening compounds, it has an advantage in that drug effects on startle potentiation are independent of memory retrieval. Further, the contextual anxiety measured in the LES test could be more relevant for pathological anxiety than the conditioned fear associated with the FPS test.