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

Philipp Singer, Detlev Boison, Hanns Möhler, Joram Feldon, Benjamin K. Yee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)401-413
Number of pages13
JournalEuropean Neuropsychopharmacology
Volume21
Issue number5
DOIs
StatePublished - May 2011
Externally publishedYes

Funding

FundersFunder number
Swiss Federal Institute of Technology
National Institutes of Health
National Institute of Mental HealthR01MH083973
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung3100AO-100309, 3100A0-116719
Eidgenössische Technische Hochschule Zürich

    Keywords

    • Attention
    • Glutamate
    • Glycine
    • NMDA
    • Schizophrenia

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