The effects of lorazepam on skin conductance responses to aversive stimuli in healthy subjects

  • Martin Siepmann
  • Benjamin Heine
  • Andreas Kluge
  • Tjalf Ziemssen
  • Michael Mück-Weymann
  • Wilhelm Kirch
RESEARCH ARTICLE

Abstract

Background

Autonomic responses to aversive stimuli are widely used to model anxiolytic drug effects in healthy humans. Benzodiazepine anxiolytics dose dependently attenuate autonomic responses to aversive stimuli by their anxiolytic as well as sedative action. The present study aimed to examine the effects of non-sedative doses of lorazepam on skin cutaneous responses to aversive stimuli and subjective mood.

Methods

A randomized, double blind, cross over study of 12 healthy male volunteers aged 24 years (23–32; median; range) was carried out. Subjects received single oral doses of 0.5 and 1.0 mg lorazepam as well as placebo on three different occasions with at least 5 days in-between. Skin conductance responses (SCRs) to unpleasant pictures and noises, pupillary unrest index as well as subjective levels of anxiety were measured repeatedly before and after drug administration.

Results

SCRs were found significantly lower 2 hours following ingestion of 0.5 mg lorazepam as well as 1, 2 and 3 hours after 1.0 mg lorazepam were given as compared to baseline conditions. By contrast, administration of placebo did not influence SCRs to a significant extent. Both doses of lorazepam did not change pupillary unrest index nor subjective mood.

Conclusions

Lorazepam may attenuate SCRs to aversive stimuli without affecting vigilance nor subjective mood. Attenuation of autonomic responses to aversive stimuli may not be specific for an anxiolytic effect.

Keywords

skin-conductance responses lorazepam anxiolytic sedative subjective mood healthy subjects 

References

  1. 1.
    Agelink MW, Majewski TB, Andrich J, Mueck-Weymann M (2002) Short-term effects of intravenous benzodiazepines on autonomic neurocardiac regulation in humans: a comparison between midazolam, diazepam and lorazepam. Crit Care Med 30:997–1006PubMedCrossRefGoogle Scholar
  2. 2.
    Birket-Smith M, Hasle N, Jensen HH (1993) Electrodermal activity in anxiety disorders. Acta Psychiatr Scand 88:350–355PubMedCrossRefGoogle Scholar
  3. 3.
    Bradley MM, Lang PJ (1994) Measuring emotion: the self-assessment manikin and the semantic differential. J Behav Ther Exp Psychiatry 25:49–59PubMedCrossRefGoogle Scholar
  4. 4.
    Campbell-Sills L, Barlow DH, Brown TA, Hofmann SG (2005) Effects of suppression and acceptance on emotional responses of individuals with anxiety and mood disorders. Behav Res Ther 44:1251–1263PubMedCrossRefGoogle Scholar
  5. 5.
    Critchley HD (2002) Electrodermal responses: what happens in the brain. The Neuroscientist 8:132–142PubMedCrossRefGoogle Scholar
  6. 6.
    Egloff B, Wilhelm FH, Neubauer DH, Mauss IB, Gross JJ (2002) Implicit anxiety measure predicts cardiocascular reactivity to an evaluated public speaking task. Emotion 2:3–11PubMedCrossRefGoogle Scholar
  7. 7.
    Fahrenberg J, Foerster F (1982) Covariation and consistency of activation parameters. Biol Psychol 15:151–169PubMedCrossRefGoogle Scholar
  8. 8.
    Feldman PD, Cohen S, Lepore SJ, Matthews KA, Kamarck TW, Marsland AL (1999) Negative emotions and acute physiological responses to stress. Ann Behav Med 21:216–222PubMedCrossRefGoogle Scholar
  9. 9.
    Garcia C, Micallef J, Dubreuil D, Philippot P, Jouve E, Blin O (2000) Effects of lorazepam on emotional reactivity, performance, and vigilance in subjects with high or low anxiety. J Clin Psychopharmacol 20:226–233PubMedCrossRefGoogle Scholar
  10. 10.
    Gibson SJ (1997) The measurement of mood states in older adults. J Gerontol: Psychol Sci 52B:P167–P174Google Scholar
  11. 11.
    Graeff FG, Parente A, Del-Ben CM, Guimaraes FS (2003) Pharmacology of human experimental anxiety. Braz J Med Biol Res 36:421–432PubMedCrossRefGoogle Scholar
  12. 12.
    Graham SJ, Scaife JC, Langley RW, et al. (2005) Effects of lorazepam on fear-potentiated startle responses in man. J Psychopharmacol 19:249–258PubMedCrossRefGoogle Scholar
  13. 13.
    Hariri AR, Mattay VS, Tessitore A, Fera F, Weinberger DR (2003) Neocortical modulation of the amygdale response to fearful stimuli. Biol Psychiatry 53:494–501PubMedCrossRefGoogle Scholar
  14. 14.
    Huwe S, Hennig J, Netter P (1998) Biological, emotional, behavioural, and coping reactions to examination stress in high and low state anxiety subjects. Anxiety Stress Copin 11:47–65CrossRefGoogle Scholar
  15. 15.
    Jalava KM, Mattila MJ, Tarssanen M, Vanakoski J (1995) Lorazepam and diazepam differently impair divided attention. Pharmacol Biochem Behav 51:189–197PubMedCrossRefGoogle Scholar
  16. 16.
    Merritt SL, Keegan AP, Mercer PW (1994) Artifact management in pupillometry. Nursing Res 43:56–59CrossRefGoogle Scholar
  17. 17.
    Newman J, Broughton R (1991) Pupillometric assessment of excessive daytime sleepiness in narcolepsy-cataplexy. Sleep 14:121–129PubMedGoogle Scholar
  18. 18.
    Nutt DJ (1990) The pharmacology of human anxiety. Pharmac Ther 47: 233–266CrossRefGoogle Scholar
  19. 19.
    O’Connell RG, Bellgrove MA, Dockree PM, Robertson IH (2004) Reduced electrodermal response to errors predicts poor sustained attention performance in attention deficit hyperactivity disorder. Neuroreport 15:2535–2538PubMedCrossRefGoogle Scholar
  20. 20.
    Phillips MA, Bitsios P, Szabadi E, Bradshaw CM (2000) Comparison of the antidepressants reboxetine, fluvoxamine and amitriptyline upon spontaneous pupillary fluctuations in healthy human volunteers. Psychopharmacology 149:72–76PubMedCrossRefGoogle Scholar
  21. 21.
    Schwerdtfeger A, Schmukle SC, Egloff B (2006) Verbal-autonomic response dissociations as traits. Biol Psychiatry 72:213–221CrossRefGoogle Scholar
  22. 22.
    Siepmann M, Handel J, Mück-Weymann M, Kirch W (2004) The effects of moclobemide on autonomic and cognitive functions in healthy volunteers. Pharmacopsychiatry 37:81–87PubMedCrossRefGoogle Scholar
  23. 23.
    Spielberger C, Gorsuch R, Lushene R (eds) (1970) STAI, manual for the state-trait-anxiety-inventory. Consulting psychologist press, Paolo AltoGoogle Scholar
  24. 24.
    Wilhelm H, Lüdtke H, Wilhelm B (1998) Pupillographic sleepiness testing in hypersomniacs and normals. Grafe’s Arch Clin Exp Ophtalmol 236:725–729CrossRefGoogle Scholar
  25. 25.
    Wright RA, Kirby LD (2003) Cardiovascular correlates of challenge and threat appraisals: a critical examination of the biopsychosocial analysis. Pers Soc Psych Rev 7:216–233CrossRefGoogle Scholar
  26. 26.
    Yoss RE, Moyer NJ, Hollenhorst RW (1970) Pupil size and spontaneous papillary waves associated with alertness, drowsiness, and sleep. Neurology 20:545–554PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Martin Siepmann
    • 1
  • Benjamin Heine
    • 1
  • Andreas Kluge
    • 1
  • Tjalf Ziemssen
    • 2
  • Michael Mück-Weymann
    • 3
  • Wilhelm Kirch
    • 1
  1. 1.Institute of Clinical Pharmacology, Medical Faculty, Technical UniversityDresdenGermany
  2. 2.Autonomic Laboratory, Department of NeurologyMedical Faculty, Technical UniversityDresdenGermany
  3. 3.Clinic for Psychotherapy and Psychosomatic Medicine, Medical Faculty, Technical UniversityDresdenGermany

Personalised recommendations