Sensitivity of late-latency auditory and somatosensory evoked potentials to threat of electric shock and the sedative drugs diazepam and diphenhydramine in human volunteers

Abstract

Late-latency auditory and somatosensory evoked potentials are sensitive to some centrally acting drugs and to certain psychological interventions. In this experiment we compared the effects of acute doses of a benzodiazepine, diazepam and an H₁ histamine receptor-blocking sedative, diphenhydramine, on auditory and somatosensory evoked potentials within the latency range 100–500ms in a fear conditioning paradigm.

Twelve healthy males (18–30 years) participated in three sessions at weekly intervals in which they received diazepam 10mg, diphenhydramine 75mg and placebo in a balanced, double-blind, crossover protocol. One hundred and twenty min after diphenhydramine or 60min after diazepam, they underwent an 8min recording period in which auditory evoked potentials elicited by 40ms, 95dB[A], 1kHz tones, and somatosensory evoked potentials elicited by a mildly painful electric shock (1.8mA, 50ms) were recorded at Cz (vertex). Each session consisted of four blocks of trials in which either the sound pulse or the shock was presented. Alternate blocks were designated SAFE or THREAT (‘context’ conditions); in THREAT blocks subjects were warned that shocks would be delivered via electrodes placed on the wrist (electrodes were removed during SAFE blocks). In one SAFE and one THREAT block, the sound stimuli and shocks (shocks were delivered only in the THREAT block) were preceded by a 2s conditioned stimulus (CS: a red light) (‘cue’ condition).

Diazepam, but not diphenhydramine, reduced the amplitude of the P2 auditory evoked potential. The THREAT context was associated with increased N1 and reduced N2 potential amplitudes. The CS had no effect on the amplitudes, but markedly reduced the latencies of the N1, P2 and N2 potentials under the THREAT condition. Diazepam reduced the amplitudes of the somatosensory potential evoked by the shock; the CS shortened the latencies of the later components of the response. Diazepam and diphenhydramine were approximately equi-sedative in the doses used in this experiment, as judged by visual analogue self-rating scales.

The results indicate that the suppression of late-latency auditory and somatosensory evoked potentials by diazepam is not simply a reflection of sedation. Late-latency evoked potentials can be modified by an aversive CS, but the components that are sensitive to the CS are different from those that are sensitive to diazepam.