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

Michele Bellesi (1) , Fiorenzo Conti (1)

1 Neuroscience

The main glutamate transporter GLT-1 is responsible for clearing synaptically released glutamate from the extracellular space and contributes to shape glutamatergic transmission. Recently, it has been shown that ceftriaxone (CEF)-induced GLT-1 up-regulation is associated to 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 of hippocampal mGluR2/3-dependent long term depression (LTD). Here, we tested the hypothesis that administration of the mGluR2/3 agonist LY379268 blocks the effect of GLT-1 up-regulation on PPI of the startle. We showed that LY379268 (1 mg/Kg) administration prevented PPI alterations associated to GLT-1 up-regulation, suggesting that CEF-induced PPI impairment was mGluR2/3-dependent. In addition, we demonstrated that CEF-induced GLT-1 up-regulaton did not alter the expression of mGluR2/3, and that it occurred at sites of mGluR2/3 expression. These results indicate a novel mechanism by which GLT-1 up-regulation modulates PPI of the startle.

Mots clés: Glutamate; Neurochemistry; Schizophrenia/Antipsychotics; Transporters; glutamate transporters; GLT-1; MEtabotropic glutamate receptors; Prepulse inhibition of the startle reflex

Michele Bellesi, Fiorenzo Conti. The mGluR2/3 agonist LY379268 blocks the effects of GLT-1 up-regulation on prepulse inhibition of the startle reflex in adult rats. Neuropsychopharmacology, 2010, n/a (n/a), pp.n/a-n/a. ⟨10.1038/npp.2009.225⟩. ⟨hal-00501997⟩