title: High-dose glycine inhibits the loudness dependence of the auditory evoked potential (LDAEP) in healthy humans.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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 C(Z).
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biological Psychiatry Research Unit, Brain Sciences Institute, Swinburne University of Technology, Melbourne, Australia. boneill@groupwise.swin.edu.au
authors.forename: Barry V
authors.initials: BV
authors.lastname: O'Neill
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Croft
authors.forename: Sumie
authors.initials: S
authors.lastname: Leung
authors.forename: Chris
authors.initials: C
authors.lastname: Oliver
authors.forename: K Luan
authors.initials: KL
authors.lastname: Phan
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods / Q000523:psychology; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000502:physiology; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology*; D018684:Glycine Agents / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013016:Sound; D011795:Surveys and Questionnaires
chemical_list: D018684:Glycine Agents; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine