The mGluR2/3 agonist LY379268 blocks the effects of GLT-1 upregulation on prepulse inhibition of the startle reflex in adult rats

Michele Bellesi, Fiorenzo Conti

Research output: Contribution to journalArticle

Abstract

The main glutamate transporter GLT-1 is responsible for clearing synaptically released glutamate from the extracellular space and contributes to the shaping of glutamatergic transmission. Recently, it has been shown that ceftriaxone (CEF)-induced GLT-1 upregulation is associated with an impairment of the prepulse inhibition (PPI) of the startle reflex, a simple form of information processing that is reduced in schizophrenia, and determines a strong reduction in hippocampal metabotropic glutamate receptor (mGluR)2/3-dependent long-term depression. In this study, we tested the hypothesis that administration of the mGluR2/3 agonist LY379268 blocks the effect of GLT-1 upregulation on PPI of the startle. We showed that administration of LY379268 (1 mg/kg) prevented PPI alterations associated with GLT-1 upregulation, suggesting that CEF-induced PPI impairment was mGluR2/3 dependent. In addition, we showed that CEF-induced GLT-1 upregulaton did not alter the expression of mGluR2/3, and also that it occurred at sites of mGluR2/3 expression. These results indicate a novel mechanism by which GLT-1 upregulation modulates PPI of the startle.

Original languageEnglish
Pages (from-to)1253-1260
Number of pages8
JournalNeuropsychopharmacology
Volume35
Issue number6
DOIs
Publication statusPublished - May 2010

Keywords

  • GLT-1
  • Glutamate transporters
  • Metabotropic glutamate receptors
  • Prepulse inhibition

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology

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