Interactions between the glycine transporter 1(GlyT1) inhibitor SSR504734 and psychoactive drugs in mouse motor behaviour

Philipp Singer, Joram Feldon, Kay Yan Benjamin Yee

Research output: Journal article publicationJournal articleAcademic researchpeer-review

23 Citations (Scopus)

Abstract

The specific glycine transporter 1 (GlyT1) inhibitor, SSR504734, is highly effective in enhancing N-methyl-d-aspartate receptor (NMDAR) function by elevating the availability of the NMDAR co-agonist, glycine, in the vicinity of NMDAR-containing glutamatergic synapses. According to the glutamatergic hypofunction hypothesis of schizophrenia, SSR504734 may therefore possess antipsychotic potential. Here, we evaluated the effects of SSR504734 in response to three psychomimetic drugs: phencyclidine, amphetamine, and apomorphine in male C57BL/6 mice. SSR504734 attenuated phencyclidine-induced (5 mg/kg, i.p.) hyperlocomotion, but potentiated the motor stimulant and motor depressant effects of amphetamine (2.5 mg/kg, i.p.) and apomorphine (0.75 mg/kg, s.c.), respectively. Hence, SSR504734 not only confers resistance to NMDAR blockade, but also enhances the locomotor response to dopaminergic stimulation. The latter finding adds to reports that SSR504734 may modulate dopamine-mediated behaviour by interference with normal glutamate-dopamine interaction. The specificity of this action of SSR504734 will be highly relevant to its potential application as an antipsychotic agent. and ECNP.
Original languageEnglish
Pages (from-to)571-580
Number of pages10
JournalEuropean Neuropsychopharmacology
Volume19
Issue number8
DOIs
Publication statusPublished - 1 Aug 2009
Externally publishedYes

Keywords

  • Amphetamine;
  • Antipsychotic;
  • Dopamine;
  • Glycine;
  • NMDA;
  • Schizophrenia

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology

Cite this