Oral administration of glycine increases extracellular serotonin but not dopamine in the prefrontal cortex of rats

Psychiatry Clin Neurosci. 2011 Mar;65(2):142-9. doi: 10.1111/j.1440-1819.2010.02181.x.


Aim: Glycine, one of the non-essential amino acids, has been reported to be effective in reducing negative symptoms of schizophrenia. Recently, we found that glycine improves subjective sleep quality in humans. The aim of this study was to investigate the effects of oral glycine administration on endogenous 5-hydroxytryptamine (5-HT) and dopamine in the prefrontal cortex (PFC) of living rats.

Methods: Microdialysis probes were inserted stereotaxically into the rat prefrontal cortex. Cortical levels of 5-HT and dopamine were measured following oral administration of 1 or 2 g/kg glycine, 2 g/kg d-serine, or 2 g/kg L-serine.

Results: Both glycine and d-serine significantly increased extracellular 5-HT levels for 10 min, whereas dopamine levels remained unchanged. L-serine, in contrast, had no significant effects on 5-HT levels.

Conclusions: It is possible that the increase in 5-HT in response to glycine and d-serine was mediated by N-methyl-D-aspartate receptors. The transient increase in 5-HT in the PFC might be associated with the alleviation of negative symptoms in patients with schizophrenia and the amelioration of sleep quality in patients with insomnia.

MeSH terms

  • Administration, Oral
  • Animals
  • Dopamine / metabolism*
  • Extracellular Space / metabolism
  • Glycine / administration & dosage
  • Glycine / cerebrospinal fluid
  • Glycine / pharmacology*
  • Male
  • Microdialysis
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Wistar
  • Serine / administration & dosage
  • Serine / pharmacology
  • Serotonin / metabolism*


  • Serotonin
  • Serine
  • Glycine
  • Dopamine