Effects of quetiapine and haloperidol on prepulse inhibition of the acoustic startle (eyeblink) response and the N1/P2 auditory evoked response in man.
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 (PPI). Here, we report the effects of the 'atypical' antipsychotic drug quetiapine and the 'conventional' antipsychotic haloperidol on these responses. Sixteen males (aged 19-38 years) participated in four sessions at 7-day intervals, in which they received quetiapine 12.5 mg, quetiapine 25 mg, haloperidol 3 mg and placebo, according to a balanced double-blind design. Electromyographic (EMG) responses of the orbicularis oculi muscle and N1/P2 auditory evoked potentials were recorded in a 20-min session, 2 h after treatment. Subjects received 40 trials in which 1-kHz sounds were presented: (i) 40 ms, 115 dB ('pulse alone' trials) and (ii) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse' trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage PPI was calculated. Serum prolactin was measured after each treatment, and autonomic (heart rate, blood pressure, salivation) and psychological (visual analogue self-ratings of mood and alertness, critical flicker fusion frequency) measures were taken before and after each treatment. Quetiapine 12.5 mg and 25 mg significantly reduced the amplitude of the EMG response without altering its inhibition by prepulses; haloperidol had no effect on EMG response amplitude or PPI. Neither drug affected N1/P2 amplitude or PPI of this response. Quetiapine, but not haloperidol, reduced subjective alertness and critical flicker fusion frequency. Haloperidol, but not quetiapine, elevated serum prolactin level. The ability of quetiapine to attenuate the startle response may reflect its sedative action.
Graham
S J
SJ
Division of Psychiatry, University of Nottingham, Nottingham, UK.
Scaife
J C
JC
Balboa Verduzco
A M
AM
Langley
R W
RW
Bradshaw
C M
CM
Szabadi
E
E
D000161:Acoustic Stimulation; D000284:Administration, Oral; D000328:Adult; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology; D001767:Blinking / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002214:Capsules; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004576:Electromyography / Q000379:methods; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000502:physiology; D005425:Flicker Fusion / Q000187:drug effects / Q000502:physiology; D006220:Haloperidol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012472:Salivation / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D002214:Capsules; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D011388:Prolactin; D006220:Haloperidol