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

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Abstract

Rationale

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.

Objectives

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.

Results

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).

Conclusion

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.

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Acknowledgments

Authors would like to thank Dr Susan Illic for performing medical examinations. The study was supported by a research grant to PJN from Blackmore’s, Australia. Fellowship support for PJN was provided by the National Health and Medical Research Council (NHMRC) of Australia (Grant 345709).

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Authors and Affiliations

  1. Biological Psychiatry Research Unit, Brain Sciences Institute, Swinburne University of Technology, Melbourne, Australia

    Barry V. O’Neill, Rodney J. Croft & Sumie Leung

  2. Behavioural Neuroscience Laboratory, School of Psychology, Psychiatry, Psychological Medicine, Monash University, Building 17, Clayton, 3800, VIC, Australia

    Barry V. O’Neill, Rodney J. Croft, K. Luan Phan & Pradeep J. Nathan

  3. School of Natural and Complementary Medicine, Southern Cross University, Lismore, NSW, Australia

    Chris Oliver

  4. Brain Imaging and Emotions Lab (BIEL) Department of Psychiatry, The University of Chicago, Chicago, IL, USA

    K. Luan Phan

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  1. Barry V. O’Neill
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  2. Rodney J. Croft
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  4. Chris Oliver
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Correspondence to Barry V. O’Neill or Pradeep J. Nathan.

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O’Neill, B.V., Croft, R.J., Leung, S. et al. High-dose glycine inhibits the loudness dependence of the auditory evoked potential (LDAEP) in healthy humans. Psychopharmacology 195, 85–93 (2007). https://doi.org/10.1007/s00213-007-0870-4

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  • DOI: https://doi.org/10.1007/s00213-007-0870-4

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