, Volume 195, Issue 1, pp 85–93

High-dose glycine inhibits the loudness dependence of the auditory evoked potential (LDAEP) in healthy humans

Original Investigation

DOI: 10.1007/s00213-007-0870-4

Cite this article as:
O’Neill, B.V., Croft, R.J., Leung, S. et al. Psychopharmacology (2007) 195: 85. doi:10.1007/s00213-007-0870-4



The loudness dependence of the auditory evoked Potential (LDAEP) has been suggested to be a putative marker of central serotonin function, with reported abnormalities in clinical disorders presumed to reflect serotonin dysfunction. Despite considerable research, very little is known about the LDAEP’s sensitivity to other neurotransmitter systems.


Given the role of N-methyl-d-aspartate (NMDA) receptors in modulating pyramidal cell activity in cortico-cortico and thalamo-cortical loops, we examined the effect of targeting the glycine modulatory site of the NMDA receptor with high-dose glycine on the LDAEP in healthy subjects.

Materials and methods

The study was a double-blind, placebo-controlled repeated-measures design in which 14 healthy participants were tested under two acute treatment conditions, placebo and oral glycine (0.8 g/kg). Changes in the amplitude of the N1/P2 at varying intensities (60, 70, 80, 90, 100 dB) were examined at CZ.


Compared to placebo, high-dose glycine induced a weaker LDAEP (a pronounced decrease in the slope of the N1/P2 with increasing tone loudness; p < 0.02).


While the exact mechanism responsible for the effects of glycine on the LDAEP are not known, the findings suggest an inhibitory effect in the cortex, possibly via activation of NMDA receptors on GABA interneurons or inhibitory glycine receptors. The findings add to the growing literature exhibiting modulation of the LDAEP by multiple neurochemical systems in addition to the serotonergic system.


Glycine NMDA receptor Glutamate Glycine receptor Loudness dependence auditory-evoked potentials LDAEP Electrophysiology Biological marker Serotonin 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Barry V. O’Neill
    • 1
    • 2
  • Rodney J. Croft
    • 1
    • 2
  • Sumie Leung
    • 1
  • Chris Oliver
    • 3
  • K. Luan Phan
    • 2
    • 4
  • Pradeep J. Nathan
    • 2
  1. 1.Biological Psychiatry Research Unit, Brain Sciences InstituteSwinburne University of TechnologyMelbourneAustralia
  2. 2.Behavioural Neuroscience Laboratory, School of Psychology, Psychiatry, Psychological MedicineMonash UniversityClaytonAustralia
  3. 3.School of Natural and Complementary MedicineSouthern Cross UniversityLismoreAustralia
  4. 4.Brain Imaging and Emotions Lab (BIEL) Department of PsychiatryThe University of ChicagoChicagoUSA

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