GABA-A and 5-HTIA receptor agonists block expression of fear-potentiated startle in mice

Abstract

The present experiments characterized the acquisition of fear-potentiated startle (FPS) and determined the sensitivity of FPS to anxiolytic compounds in DBA/1J mice. A light (30 s) conditioned stimulus (CS) and mild footshock (0.14 mA, 0.5 s) unconditioned stimulus (US)were used. First, acquisition of FPS was examined by presenting the acoustic startle probe during and after each CS-US pairing trial, allowing for a trial-by-trialmeasurement of experience-dependent startle plasticity. In this novelprotocol, mice showed robust acquisition(larger acoustic startle reflex in the presence ofthe CS) of FPS after as few as eight CS-US pairings. FPS was significantly greater when theCS and US were paired explicitly (light-paired) as compared to when both the US and CS were presented randomly (unpaired), or whenthe CS was presented alone (no shock), indicating pairing-dependent learning of the CS. Second, the present study assessed thesensitivity of FPS in miceto anxiolytic drugs. The GABA-A receptor agonists diazepam (3 and 6 mg/kg) and chlordiazepoxide (10mg/kg)significantly reduced the expression of FPS post-training, as did the serotonin IA receptor partialagonistbuspirone (5 and 10 mg/kg).Furthermore, allthree anxiolytic drugs reduced startle responding in a cue-specific manner and without significant changes in baselineresponding. These data demonstrate a novelmethod of studying acquisition of FPS, and supportthe predictive validity ofthe FPS modelof anxiolytic drug action in mice. © 2003 American College of Neuropsychopharmacology.