Regulation of cognition and symptoms of psychosis: Focus on GABAA receptors and glycine transporter 1`

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

Research output: Contribution to journalReview articlepeer-review

Abstract

Adaptive purposeful behaviour depends on appropriate modifications of synaptic connectivity that incorporate an organism's past experience. At least some forms of such synaptic plasticity are believed to be mediated by NMDA receptors (NMDARs). Complementary interaction with inhibitory neurotransmission mediated by GABAA receptors, and upstream control of the excitability of NMDARs by glycine availability can greatly influence the efficacy of NMDAR mediated neuroplasticity, and thereby exert significant effects on cognition. Memory, selective attention or sensorimotor gating functions can be modified in mice with a reduction of α5GABAA receptors in the hippocampus or a selective deletion of glycine transporter 1 (GlyT1) in the forebrain. Both genetic manipulations altered the formation or persistence of associative links leading to distinct phenotypes on trace conditioning, extinction learning, latent inhibition, working memory, and object recognition. Behavioural assays of latent inhibition, prepulse inhibition, working memory, and sensitivity to psychostimulants in particular suggest that α3 and α5 subunit-containing GABAA receptors as well as GlyT1 are potential sites for ameliorating psychotic-like behaviour. Taken together, these results qualify distinct GABA-A receptor subtypes and GlyT1 as molecular targets for the development of a new pharmacology in the treatment of cognitive decline and psychotic symptoms.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume90
Issue number1
DOIs
StatePublished - Jul 2008
Externally publishedYes

Keywords

  • Anxiety
  • Cognition
  • GABA receptors
  • Glycine transporter 1
  • Memory and learning
  • Pychosis

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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