The neurotensin-1 receptor agonist PD149163 blocks fear-potentiated startle

Preliminary evidence suggests that the neuropeptide, neurotensin (NT) may regulate fear/anxiety circuits. We investigated the effects of PD149163, a NT1 receptor agonist, on fear-potentiated startle (FPS). Sprague Dawley rats were trained to associate a white light with a mild foot shock. In one experiment, animals were treated with either subcutaneous vehicle or PD149163 (0.01, 0.1 or 1.0 mg/kg) 24 h after training. Twenty minutes later their acoustic startle response in the presence or absence of the white light was tested. In a second experiment, saline and 1.0 mg/kg PD149163 were tested using a separate group of rats. In the first experiment, PD149163 produced a non-significant decrease in baseline acoustic startle at all three doses. As expected, saline-treated rats exhibited significant FPS. An ANOVA of percentage FPS revealed no significant effect of treatment group overall but the high dose group did not display FPS strongly suggesting an FPS effect at this dose. This finding was confirmed in the second experiment where the high dose of PD149163 reduced percent FPS relative to saline (P < 0.05). These data suggest that systemically administered NT1 agonists modulate the neural circuitry that regulates fear and anxiety to produce dose-dependent anxiolytic-like effects on FPS.