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Benzodiazepines have no effect on fear-potentiated startle in humans.
Psychopharmacology (Berl). 2002 May; 161(3):233-47.P

Abstract

RATIONALE

Pre-clinical and clinical investigations have provided a great deal of evidence that the fear-potentiated startle paradigm represents a valid model for the objective assessment of emotional states of anxiety and fear.

OBJECTIVE

The four studies presented in this report sought to further validate the "threat of shock" paradigm as a human analogue to fear-potentiated startle in rats, by examining the effect of benzodiazepine administration on both baseline and fear-potentiated startle.

METHODS

Three studies, conducted at Utrecht University, evaluated the effects of oxazepam and of diazepam on baseline and fear-potentiated startle, whereas a fourth study, conducted at Yale University, evaluated the effect of diazepam on baseline, contextual and cue-specific fear-potentiated startle. The threat of shock paradigm consisted of verbal instruction about two visual cues (the threat cue predicted the possible administration of electric shock, the other predicted a safe period), followed by a series of presentations of these cues. During these conditions, acoustic startle stimuli were presented in order to elicit startle responses. The magnitude of the startle response was used to index the degree of fear or alarm experienced during the periods of threat and safety. The fourth study examined the effect of IV administration of diazepam in a similar threat of shock paradigm except that there were two additional context manipulations: electrode placement and darkness.

RESULTS

None of the drug manipulations affected specific threat-cue potentiation of startle. However, reductions in baseline startle were observed. Further, startle potentiation by darkness was inhibited by diazepam.

CONCLUSIONS

At least one type of fear-potentiated startle, i.e. potentiation by a cue-specific fear manipulation, is not susceptible to benzodiazepine treatment. In contrast, effects of manipulations more akin to anxiety (darkness, context) appear sensitive to benzodiazepines. Human experimental models differentiating between these cue specific and contextual responses are needed to shed more light on differences in the anatomy and pharmacology of anxiety disorders.

Authors+Show Affiliations

Mood and Anxiety Disorder Program, NIMH, NIH, 15k North Drive MSC 2670, Bethesda, MD 20892, USA. baasj@intra.nimh.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Controlled Clinical Trial
Journal Article

Language

eng

PubMed ID

12021826

Citation

Baas, Johanna M P., et al. "Benzodiazepines Have No Effect On Fear-potentiated Startle in Humans." Psychopharmacology, vol. 161, no. 3, 2002, pp. 233-47.
Baas JM, Grillon C, Böcker KB, et al. Benzodiazepines have no effect on fear-potentiated startle in humans. Psychopharmacology (Berl). 2002;161(3):233-47.
Baas, J. M., Grillon, C., Böcker, K. B., Brack, A. A., Morgan, C. A., Kenemans, J. L., & Verbaten, M. N. (2002). Benzodiazepines have no effect on fear-potentiated startle in humans. Psychopharmacology, 161(3), 233-47.
Baas JM, et al. Benzodiazepines Have No Effect On Fear-potentiated Startle in Humans. Psychopharmacology (Berl). 2002;161(3):233-47. PubMed PMID: 12021826.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Benzodiazepines have no effect on fear-potentiated startle in humans. AU - Baas,Johanna M P, AU - Grillon,Christian, AU - Böcker,Koen B E, AU - Brack,Anouk A, AU - Morgan,Charles A,3rd AU - Kenemans,J Leon, AU - Verbaten,Marinus N, Y1 - 2002/03/20/ PY - 2001/06/20/received PY - 2002/01/04/accepted PY - 2002/5/22/pubmed PY - 2003/1/14/medline PY - 2002/5/22/entrez SP - 233 EP - 47 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 161 IS - 3 N2 - RATIONALE: Pre-clinical and clinical investigations have provided a great deal of evidence that the fear-potentiated startle paradigm represents a valid model for the objective assessment of emotional states of anxiety and fear. OBJECTIVE: The four studies presented in this report sought to further validate the "threat of shock" paradigm as a human analogue to fear-potentiated startle in rats, by examining the effect of benzodiazepine administration on both baseline and fear-potentiated startle. METHODS: Three studies, conducted at Utrecht University, evaluated the effects of oxazepam and of diazepam on baseline and fear-potentiated startle, whereas a fourth study, conducted at Yale University, evaluated the effect of diazepam on baseline, contextual and cue-specific fear-potentiated startle. The threat of shock paradigm consisted of verbal instruction about two visual cues (the threat cue predicted the possible administration of electric shock, the other predicted a safe period), followed by a series of presentations of these cues. During these conditions, acoustic startle stimuli were presented in order to elicit startle responses. The magnitude of the startle response was used to index the degree of fear or alarm experienced during the periods of threat and safety. The fourth study examined the effect of IV administration of diazepam in a similar threat of shock paradigm except that there were two additional context manipulations: electrode placement and darkness. RESULTS: None of the drug manipulations affected specific threat-cue potentiation of startle. However, reductions in baseline startle were observed. Further, startle potentiation by darkness was inhibited by diazepam. CONCLUSIONS: At least one type of fear-potentiated startle, i.e. potentiation by a cue-specific fear manipulation, is not susceptible to benzodiazepine treatment. In contrast, effects of manipulations more akin to anxiety (darkness, context) appear sensitive to benzodiazepines. Human experimental models differentiating between these cue specific and contextual responses are needed to shed more light on differences in the anatomy and pharmacology of anxiety disorders. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/12021826/Benzodiazepines_have_no_effect_on_fear_potentiated_startle_in_humans_ L2 - https://dx.doi.org/10.1007/s00213-002-1011-8 DB - PRIME DP - Unbound Medicine ER -