Regulation of Editing and Expression of Glutamate α-Amino-Propionic-Acid (AMPA)/Kainate Receptors by Antidepressant Drugs

• Published in: Biological psychiatry (1969) Vol. 59; no. 8; pp. 713 - 720
• Main Authors: Barbon, Alessandro, Popoli, Maurizio, La Via, Luca, Moraschi, Stefania, Vallini, Ivan, Tardito, Daniela, Tiraboschi, Ettore, Musazzi, Laura, Giambelli, Roberto, Gennarelli, Massimo, Racagni, Giorgio, Barlati, Sergio
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.04.2006; Elsevier Science
• Subjects: Animals; antidepressant; Antidepressive Agents - pharmacology; Biological and medical sciences; Brain - anatomy & histology; Brain - drug effects; Brain - metabolism; expression; Gene Expression - drug effects; Glutamate receptors; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, AMPA - classification; Receptors, AMPA - genetics; Receptors, AMPA - metabolism; Receptors, Kainic Acid - classification; Receptors, Kainic Acid - genetics; Receptors, Kainic Acid - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA editing; RNA Editing - drug effects; RNA, Messenger - metabolism; Glutamate receptors; RNA editing; expression; antidepressant; Psychotropic; Propionic acid; Rodentia; Rattus norvegicus; Glutamate receptor; Gene expression; Glutamate; Kainate receptor; Vertebrata; Chemotherapy; AMPA receptor; Mammalia; Treatment; Excitatory aminoacid; Neurotransmitter; Antidepressant agent
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2005.10.018

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. 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. 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. 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.