Differential effects of alprazolam on the baseline and fear-potentiated startle reflex in humans:: a dose-response study

Rationale: The "fear-potentiated startle" paradigm has been extensively used in animal studies, and more recently in human experimental psychopharmacology to evaluate the effects of anxiogenic and anxiety-relieving drugs. Previous human studies have shown that both the baseline and the fear-potentiated responses can be inhibited by anxiety-relieving drugs, suggesting drug activity on two different emotional states, the former reflecting a resting condition and the latter more akin to pathological anxiety. Objectives: To examine to which extent the reductions induced by a benzodiazepine on the basic and the fear-potentiated startle responses are of equal intensity, and whether or not the drug shows a predominant, i.e., selective, effect on either. Methods: The effects of three increasing doses of the benzodiazepine alprazolam (0.25, 0.5, and 1.0 mg) were assessed on the human baseline and fear-potentiated startle responses. Twelve healthy volunteers attended the laboratory on four experimental days and received either alprazolam or placebo according to a double-blind crossover balanced design. Startle recordings were undertaken 2 h after drug intake. Fear potentiation was implemented by means of an electric-shock-anticipation experimental procedure. Additionally, subjective self-reports of sedation and anxiety and psychomotor performance were obtained at 2 and 3 h, respectively, after drug administration. Results: Alprazolam dose-dependently impaired psychomotor performance and produced increases in subjective anxiolytic activity and sedation, although the latter did not reach statistical significance. Additionally, the drug reduced the magnitude of the startle response both in the absence and in the presence of a threat-related cue, although a differentially greater inhibitory effect was seen on the fear-potentiated response as the dose increased. Conclusions: Alprazolam showed a greater inhibitory effect on the fear-potentiated startle than on the baseline reflex, suggesting a more selective action of the drug on those structures mediating potentiation of the behavioral response by anxiety.