Acute high-dose glycine attenuates mismatch negativity (MMN) in healthy human controls.
BACKGROUND
Schizophrenia is commonly associated with impairments in pre-attentive change detection as represented by reduced mismatch negativity (MMN). The neurochemical basis of MMN has been linked to N-methyl-D: -aspartate (NMDA) receptor function. Glycine augments NMDA receptor function via stimulation of the glycine modulatory site of the NMDA receptor and has been shown to effectively reduce negative symptoms in schizophrenia. However, no study has investigated the possible effects of high-dose glycine on MMN. Further, the physiological consequences of administering high-dose glycine in subjects with normal NMDA receptor function are unknown.


OBJECTIVE
The aim of the present project was to investigate the acute effects of a single large dose of glycine on the human MMN in healthy subjects.


METHODS
Sixteen healthy male subjects participated in a double blind, placebo-controlled, crossover design in which each subject was tested under two acute treatment conditions separated by a 1-week washout period; placebo and 0.8 g/kg glycine. The subjects were exposed to a duration-MMN paradigm with 50-ms standard tones (91%) and 100-ms deviant tones (9%).


RESULTS
The results showed that glycine significantly attenuated duration MMN amplitude at frontal electrodes. There was no effect of glycine on MMN latencies or on amplitudes or latencies of N1, N2 and P3a.


CONCLUSIONS
These findings suggest that an acute high dosage of glycine attenuates MMN in healthy controls, raising the possibility that optimal effects of glycine and other glycine agonists may depend on the integrity of the NMDA receptor system.
Leung
Sumie
S
Brain Sciences Institute, Swinburne University of Technology, Melbourne, Australia.
Croft
Rodney J
RJ
O'Neill
Barry V
BV
Nathan
Pradeep J
PJ
D000161:Acoustic Stimulation; D000328:Adult; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004594:Electrophysiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; 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 / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000503:physiopathology
D018684:Glycine Agents; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine