4.7 Article

The mGluR2/3 Agonist LY379268 Blocks the Effects of GLT-1 Upregulation on Prepulse Inhibition of the Startle Reflex in Adult Rats

Journal

NEUROPSYCHOPHARMACOLOGY
Volume 35, Issue 6, Pages 1253-1260

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2009.225

Keywords

glutamate transporters; GLT-1; metabotropic glutamate receptors; prepulse inhibition

Funding

  1. MIUR
  2. Universita Politecnica delle Marche

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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. Neuropsychopharmacology (2010) 35, 1253-1260; doi: 10.1038/npp.2009.225; published online 13 January 2010

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