High-dose glycine inhibits the loudness dependence of the auditory evoked potential (LDAEP) in healthy humans
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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.
KeywordsGlycine NMDA receptor Glutamate Glycine receptor Loudness dependence auditory-evoked potentials LDAEP Electrophysiology Biological marker Serotonin
- Baribeau JC, Laurent JP (1987) The effect of selective attention on augmenting/intensity function of the early negative waves of AEP’s. Electroencephalogr Clin Neurophysiol S40:68–75Google Scholar
- Berger AJ, Dieudonne S, Ascher P (1998) Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J Physiol 80:3336–3340Google Scholar
- Gallinat J, Senkowski D, Wernicke C, Juckel G, Becker I, Sander T, Smolka M, Hegerl U, Rommelspacher H, Winterer G, Herrmann WM (2003) Allelic variants of the functional promoter polymorphism of the human serotonin transporter gene is associated with auditory cortical stimulus processing. Neuropsychopharmacology 28:530–532PubMedCrossRefGoogle Scholar
- Nathan PJ, Segrave R, Phan KL, O’Neill B, Croft RJ (2006) Direct evidence that acutely enhancing serotonin with the selective serotonin reuptake inhibitor citalopram modulates the loudness dependence of the auditory evoked potential (LDAEP) marker of central serotonin function. Hum Psychopharmacol 21:47–52PubMedCrossRefGoogle Scholar
- Palmer C, Ellis KA, O’Neill BV, Croft RJ, Leung S, Oliver C, Wesnes KA, Nathan PJ (2007) The cognitive effects of modulating the glycine site of the NMDA receptor with high-dose glycine. Hum Psychopharmacol (in press)Google Scholar
- Pogarell O, Tatsch K, Juckel G, Hamann C, Mulert C, Popperl G, Folkerts M, Chouker M, Riedel M, Zaudig M, Moller HJ, Hegerl U (2004) Serotonin and dopamine transporter availabilities correlate with the loudness dependence of auditory evoked potentials in patients with obsessive–compulsive disorder. Neuropsychopharmacology 29:1910–1917PubMedCrossRefGoogle Scholar
- Tuchtenhagen F, Daumann J, Norra C, Gobbele R, Becker S, Pelz S, Sass H, Buchner H, Gouzoulis-Mayfrank E (2000) High intensity dependence of auditory evoked dipole source activity indicates decreased serotonergic activity in abstinent ecstasy (MDMA) users. Neuropsychopharmacology 22:608–617PubMedCrossRefGoogle Scholar
- Wenthold RJ, Hunter C (1990) Immunocytochemistry of glycine and glycvine receptors in the central auditory system. In: Ottersen OP, Storm-Mathisen J (eds) Glycine neurotransmission. Wiley, New York, pp 391–416Google Scholar
- Zemon V, Kaplan E, Ratliff F (1986) The role of GABA-mediated intracortical inhibition in the generation of visual evoked potentials. In: Cracco RQ, Bodis-Wollner I (eds) Evoked potentials. Liss, New York, pp 287–295Google Scholar