Regulation of editing and expression of glutamate α-amino-propionic- acid (AMPA)/kainate receptors by antidepressant drugs

Alessandro Barbon, Maurizio Popoli, Luca La Via, Stefania Moraschi, Ivan Vallini, Daniela Tardito, Ettore Tiraboschi, Laura Musazzi, Roberto Giambelli, Massimo Gennarelli, Giorgio Racagni, Sergio Barlati

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Several reports have shown that the glutamatergic system is involved in both the pathogenesis of affective and stress-related disorders and in the action of antidepressant drugs. In particular, antidepressant treatment was shown to modulate expression and function of ionotropic glutamate receptors, to inhibit glutamate release and to restore synaptic plasticity impaired by stress. Methods: We analyzed the mRNA expression and RNA editing of α-amino-propionic-acid (AMPA) and kainate (KA) receptor subunits, in the pre-frontal/frontal cortex (P/FC) and hippocampus (HI) of rats chronically treated with three different drugs: the selective serotonin (5-HT) reuptake inhibitor fluoxetine, the selective noradrenaline (NA) reuptake inhibitor reboxetine and the tricyclic antidepressant desipramine. Results: Our data showed that fluoxetine and desipramine exerted moderate but selective effects on glutamate receptor expression and editing, while reboxetine appeared to be the drug that affects glutamate receptors (GluR) most. The most consistent effect, observed with pronoradrenergic drugs (desipramine and reboxetine), was a decrease of GluR3 expression both in P/FC and HI. Interestingly, in HI, the same drugs also decreased the editing levels of either the flip (desipramine) or flop (reboxetine) form of GluR3. Conclusions: Overall, these results point to specific and regionally discrete changes in the expression and editing level of glutamate receptors and, in particular, to a selective reduction of conductance for GluR3-containing receptors following treatment with antidepressant drugs. These data support the hypothesis that changes in glutamate neurotransmission are involved in the therapeutic effects induced by these drugs.

Original languageEnglish
Pages (from-to)713-720
Number of pages8
JournalBiological Psychiatry
Volume59
Issue number8
DOIs
Publication statusPublished - Apr 15 2006

Keywords

  • Antidepressant
  • Expression
  • Glutamate receptors
  • RNA editing

ASJC Scopus subject areas

  • Biological Psychiatry

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