Anxiogenic treatments do not increase fear-potentiated startle in mice

Abstract

In rodents, the fear-potentiated startle paradigm (FPS; exaggerated startle as a measure of the conditioned fear response to cues associated with footshock) has demonstrated predictive validity for anxiolytic drugs. The predictive validity of the model for anxiogenic drugs, however, remains unclear. Therefore, we evaluated the bi-directionality of the FPS model for anxiety-modulating compounds in mice. The clinical anxiogenics FG-7142 (1-20 mg/kg), yohimbine (.1-10 mg/kg), and m-Chlorophenylpiperazine (mCPP; .3-3 mg/kg), and the putative anxiogenics atipamezole (.3-3 mg/kg) and corticotropin-releasing factor (h/r-CRF; .03-1 microg) were tested in DBA/1J mice trained for FPS. Contrary to predictions, FG-7142 (10 and 20 mg/kg) and yohimbine (10 mg/kg) reduced FPS in mice without affecting baseline startle. Atipamezole (3 mg/kg), mCPP (3 mg/kg), and h/r-CRF (.3, 1 microg) did not affect FPS, but increased startle independently from the presence of the cue. FG-7142 and h/r-CRF had similar effects in 129SvEv mice. Murine FPS is not bi-directionally predictive for anxiety-modulating compounds, although murine baseline startle may have some utility as a bi-directional model of anxiety. These data corroborate the recent hypothesis that systems mediating FPS are independent from systems mediating increased startle from unconditioned and putatively anxiogenic stimuli.