The effects of some antidepressant drugs on prepulse inhibition of the acoustic startle (eyeblink) response and the N1/P2 auditory evoked response in man.
Both the acoustic startle (eyeblink) response and the N1/P2 complex of the auditory evoked potential can be suppressed by presentation of a brief low-intensity stimulus 30-500 ms before the 'startle-eliciting' stimulus ('prepulse inhibition', PPI). We examined the effects of three antidepressants on PPI of these two responses. Fifteen males (19-30 years) participated in four weekly sessions, in which they received placebo, amitriptyline (100 mg), fluvoxamine (100 mg), and reboxetine (4 mg) (p.o.), according to a balanced double-blind design. Twenty minute simultaneous recordings of electromyographic (EMG) responses of the orbicularis oculi muscle of the right eye and vertex auditory evoked potentials were carried out 195 min after drug ingestion. Sound stimuli (1 kHz) were presented in 40 trials separated by variable intervals (mean 25 s): (1) 40 ms, 115 dB ('pulse alone', 20 trials) and (2) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse', 20 trials). Under the placebo condition, both the EMG response and the N1/P2 complex showed >50% PPI. Fluvoxamine and reboxetine did not significantly alter the amplitude or PPI of either response. Amitriptyline significantly reduced the amplitudes of both responses; it had no effect on PPI of the EMG response, but significantly attenuated PPI of the N1/P2 complex. Amitriptyline also reduced arousal, as indicated by an increase in power of low-frequency electroencephalographic waves. The results confirm the susceptibility of the N1/P2 complex to PPI. The reduction of the amplitudes of the EMG response and N1/P2 complex by amitriptyline may be related to its sedative action. The differential effect of amitriptyline on PPI of the N1/P2 complex supports the suggestion that different mechanisms may be involved in PPI of this response and PPI of the N1/P2 complex.
Phillips
M A
MA
Division of Psychiatry, University of Nottingham, UK.
Langley
R W
RW
Bradshaw
C M
CM
Szabadi
E
E
D000284:Administration, Oral; D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000328:Adult; D000639:Amitriptyline / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects; D001288:Attention / Q000187:drug effects*; D001767:Blinking / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D016666:Fluvoxamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D000077593:Reboxetine; D013216:Reflex, Startle / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D009025:Morpholines; D000639:Amitriptyline; D000077593:Reboxetine; D016666:Fluvoxamine