Modulation of sensorimotor gating in prepulse inhibition by conditional brain glycine transporter 1 deletion in mice

Philipp Singer, Detlev Boison, Hanns Möhler, Joram Feldon, Kay Yan Benjamin Yee

Research output: Journal article publicationJournal articleAcademic researchpeer-review

9 Citations (Scopus)

Abstract

Inhibition of glycine transporter 1 (GlyT1) augments N-methyl-D-aspartate receptor (NMDAR)-mediated transmission and represents a potential antipsychotic drug target according to the NMDAR hypofunction hypothesis of schizophrenia. Preclinical evaluation of GlyT1 inhibiting drugs using the prepulse inhibition (PPI) test, however, has yielded mixed outcomes. Here, we tested for the first time the impact of two conditional knockouts of GlyT1 on PPI expression. Complete deletion of GlyT1 in the cerebral cortices confers resistance to PPI disruption induced by the NMDAR blocker MK-801 (0.2. mg/kg, i.p.) without affecting PPI expression in unchallenged conditions. In contrast, restricting GlyT1 deletion to neurons in forebrain including the striatum significantly attenuated PPI, and the animals remained sensitive to the PPI-disruptive effect of MK-801 at the same dose. These results demonstrate in mice that depending on the regional and/or cell-type specificity, deletion of the GlyT1 gene could yield divergent effects on PPI. and ECNP.
Original languageEnglish
Pages (from-to)401-413
Number of pages13
JournalEuropean Neuropsychopharmacology
Volume21
Issue number5
DOIs
Publication statusPublished - 1 May 2011
Externally publishedYes

Keywords

  • Attention
  • Glutamate
  • Glycine
  • NMDA
  • Schizophrenia

ASJC Scopus subject areas

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

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