Diazepam suppresses the acquisition but not the expression of 'fear-potentiation' of the acoustic startle response in man.
Sudden auditory stimuli elicit a short-latency muscular response (acoustic startle response) which is enhanced during presentation of a Pavlovian conditioned stimulus (CS) that has previously been paired with an aversive unconditioned stimulus (US) ('fear-potentiation'). In rodents, acute treatment with benzodiazepines blocks both the acquisition of fear-potentiation and the expression of fear-potentiation induced by prior exposure to CS/US pairing. We examined the effect of diazepam on the acquisition and expression of fear-potentiation of the acoustic startle response in man. Forty-six male volunteers (18-30 years) participated in two sessions separated by 7 days. In session 1, they were exposed to 20 2-s presentations of a light (CS), 50% of which terminated with an electric shock to the wrist (1.8 mA, 50 ms: US). Somatosensory potentials evoked by the US were recorded from the scalp at Cz, and skin conductance responses from electrodes taped to the second and fourth fingers. In session 2, the CS was presented 20 times without the US; a random 50% of CS presentations terminated with a sound pulse (40-ms 115-dB 1-kHz); an equal number of sound pulses was presented without the CS. Electromyographic responses of the orbicularis oculi muscle to the acoustic stimuli were recorded from electrodes placed on the lower eyelid, late-latency auditory evoked potentials were recorded at Cz, and skin conductance responses from electrodes taped to the second and fourth fingers. In each session, alertness was measured using visual analogue self-rating scales and critical flicker fusion frequency. Subjects received placebo or diazepam 10mg in the two sessions in a double-blind protocol: group 1 (n 12) placebo/placebo; group 2 (n 11) placebo/diazepam; group 3 (n 12) diazepam/placebo; group 4 (n 11) diazepam/diazepam. Diazepam reduced alertness as measured by visual-analogue self-rating scales and critical flicker fusion frequency. In session 1, diazepam reduced the amplitude of the somatosensory potentials and skin conductance responses evoked by the CS. In session 2, the acoustic startle response, the N1/P2 auditory evoked response and the skin conductance response evoked by the sound stimuli were enhanced in the presence of the CS. This fear-potentiation was attenuated in subjects who received diazepam in session 1, but was not affected by the treatment given in session 2. The results indicate that diazepam blocks the acquisition of fear-potentiation of startle responses in man, as in animals, but does not prevent the expression of a previously learned response.
Scaife
J C
JC
Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Nottingham, UK.
Langley
R W
RW
Bradshaw
C M
CM
Szabadi
E
E
D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects; D003463:Cues; D003975:Diazepam / Q000494:pharmacology*; D004576:Electromyography; D005072:Evoked Potentials, Auditory / Q000502:physiology; D005239:Fear / Q000523:psychology*; D005425:Flicker Fusion / Q000187:drug effects; D005712:Galvanic Skin Response / Q000187:drug effects; D006801:Humans; D008297:Male; D013216:Reflex, Startle / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D003975:Diazepam