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Effects of clonidine and diazepam on prepulse inhibition of the acoustic startle response and the N1/P2 auditory evoked potential in man

College of Applied Medical Sciences, King Saud University, Riyadh, Saudia Arabia. khayria_audio{at}hotmail.com; Division of Psychiatry, University of Nottingham, Nottingham, UK

R. W. Langley

Division of Psychiatry, University of Nottingham, Nottingham, UK

C. M. Bradshaw

Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Room B109, Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK c.m.bradshaw{at}nottingham.ac.uk

E. Szabadi

Division of Psychiatry, University of Nottingham, Nottingham, UK

Contraction of the orbicularis oculi muscle in response to a sudden loud sound (acoustic startle response) and the N1/P2 component of the auditory evoked potential are both attenuated when a brief low-intensity stimulus is presented 30–500 ms before the ‘startle-eliciting’ stimulus (prepulse inhibition). We examined the effects of two sedative/anxiolytic drugs, diazepam and clonidine, on prepulse inhibition of these two responses in healthy volunteers. Fifteen males (aged 18–35 years) participated in three sessions in which they received oral doses of placebo, diazepam 10 mg and clonidine 0.2 mg according to a balanced double-blind protocol. Thirty-minute simultaneous recordings of the electromyographic (EMG) responses of the orbicularis oculi muscle of the right eye and the vertex auditory evoked potentials took place 120 min after ingestion of clonidine and 60 min after ingestion of diazepam. Sound stimuli (1 kHz) were presented in 60 trials separated by variable intervals (mean 25 s): (i) 40-ms 115-dB (‘pulse alone’, 20 trials); (ii) 40-ms 85-dB (20 trials); (iii) 40-ms 85-dB, followed after 120 ms by 40-ms 115-dB (‘prepulse/pulse’, 20 trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage prepulse inhibition was calculated. The amplitude of the EMG response was significantly reduced both by diazepam and by clonidine; neither drug significantly altered prepulse inhibition of the EMG response. Diazepam, but not clonidine, significantly reduced the amplitude of the N1/P2 potential; neither drug significantly affected prepulse inhibition of the N1/P2 potential. Both drugs reduced self-rated alertness and anxiety, and systolic blood pressure; clonidine, but not diazepam reduced diastolic blood pressure and salivation. The results confirm previous findings that sedative drugs can suppress the startle response without affecting prepulse inhibition of this response, and provide new information on the effects of these drugs on the N1/P2 potential and its inhibition by prepulses.

Key Words: acousticstartleresponse • clonidine • diazepam • N1/P2auditoryevokedpotential • prepulseinhibition

Journal of Psychopharmacology, Vol. 15, No. 4, 237-242 (2001)
DOI: 10.1177/026988110101500402


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