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Effects of lorazepam on fear-potentiated startle responses in man

J. C. Scaife

R. W. Langley

C. M. Bradshaw

E. Szabadi

Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Nottingham, UK

L. Xi

T. Crumley

Merck Research Laboratories, Bluebell, Pennsylvania, Rahway, NJ, USA

N. Calder

Merck Research Laboratories, Terlings Park, Harlow, Essex, UK

K. Gottesdiener

J. A. Wagner

Merck Research Laboratories, Bluebell, Pennsylvania, Rahway, NJ, USA

Sudden intense sensory stimuli elicit a cascade of involuntary responses, including a short-latency skeletal muscular response (‘eyeblink startle response’) and longer-latency autonomic responses. These responses are enhanced when subjects anticipate an aversive event compared to periods when subjects are resting (‘fear potentiation’). It has been reported previously that the anxiolytic diazepam can suppress fear-potentiation of the eyeblink startle response in human volunteers. The present experiment aimed to confirm and extend these observations by examining the effect of another benzodiazepine, lorazepam, on the eyeblink and skinconductance components of the acoustic startle, and on fear-potentiation of these responses. Eighteen male volunteers participated in threeweekly sessions in which they received oral treatment with placebo, lorazepam (1 mg) and lorazepam (2 mg), according to a balanced three-period, crossover, double-blind design. Two hours after ingestion of the treatments, electromyographic responses of the orbicularis oculi muscle and skin conductance responses were evoked by sound pulses during alternating periods in which the threat of an electric shock (electrodes attached to the subject’s wrist) was present (THREAT) and absent (SAFE). The THREAT condition was associated with significant increase in the amplitude of the electromyographic (EMG) and skin conductance responses; there were also increases in baseline skin conductance, the number and amplitude of ‘spontaneous’ skin conductance fluctuations and self-rated anxiety. Lorazepam attenuated the effect of THREAT on self-rated anxiety and on the amplitude of the EMG response, but had no significant effect on fear-potentiation of the skin conductanceresponses. These results extend previous findings of the effect of diazepam on the fear-potentiated eyeblink startle response to lorazepam, and suggest that fear-potentiation of the later autonomic component of the startle response may be less sensitive to benzodiazepines than the fear-potentiated eyeblink response and self-rated anxiety.

Key Words: anxiety • fear • lorazepam • skin conductance response • startle reflex

Journal of Psychopharmacology, Vol. 19, No. 3, 249-258 (2005)
DOI: 10.1177/0269881105051528


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