Effects of clonidine and diazepam on the acoustic startle response and on its inhibition by 'prepulses' in man

This experiment examined the effects of two sedative/anxiolytic drugs, diazepam and clonidine, on the eyeblink component of the acoustic startle response in healthy volunteers. Twelve males (18-30 years), screened for normal hearing thresholds, participated in three sessions in which they received oral doses of placebo, diazepam 10 mg and clonidine 200 mu g according to a balanced double-blind protocol. Thirty-minute electromyographic recordings from the orbicularis oculi muscle of the right eye were carried out 120 min after ingestion of clonidine and 60 min after ingestion of diazepam. Subjects received 36 40-msec sound pulses (115 dB), separated by variable intervals (mean 25 sec); in 24 of the trials the pulse was preceded by a 40-msec prepulse (75 dB in 12 trials and 85 dB in 12 trials; prepulse-pulse interval, 120 msec). The amplitude of the startle response was significantly reduced both by diazepam (mean +/- SEM: -43.9 +/- 7.4%)and by clonidine (-75.7 +/- 4.7%). Under the placebo condition, the 75 and 85 dB prepulses inhibited the startle response by 38.6 +/- 6.5 and 70.3 +/- 2.9%, respectively. Neither drug significantly altered the degree of prepulse inhibition. Both drugs reduced self-rated alertness; clonidine reduced systolic blood pressure and salivation. The results confirm the suppressant effect of clonidine on the startle response and show a qualitatively similar effect of diazepam; the results also demonstrate the insensitivity of prepulse inhibition of the startle response to doses of sedative drugs that are sufficient to attenuate the startle response itself.