Modulation of noise-potentiated acoustic startle via the benzodiazepine--gamma-aminobutyric acid receptor complex.
Diazepam (DZ), an anxiolytic benzodiazepine (BZD) compound, attenuated the facilitation of the acoustic startle response by background noise. In Experiment 1, using a cumulative dosing paradigm, the effect of DZ on noise potentiation was found to be dose related. In Experiment 2, using a between-animals exposure design, the effect of DZ on noise potentiation was attenuated by coexposure to the central-type BZD receptor antagonist RO 15-1788, which itself was without effect. Using a cumulative dosing design in Experiment 3, RO 15-1788 was found to reverse the effect of DZ, whereas the peripheral-type BZD receptor ligand RO 54864 was without effect. The differences in the effect of cumulative exposure versus single dose exposure to RO 15-1788 were interpreted as indicative of either an intrinsic effect of the antagonist after repeated exposure or an influence of background noise itself on the BZD-gamma-aminobutyric acid receptor complex.