Regulation of editing and expression of glutamate alpha-amino-propionic-acid (AMPA)/kainate receptors by antidepressant drugs.
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 alpha-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.
Barbon
Alessandro
A
Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Italy.
Popoli
Maurizio
M
La Via
Luca
L
Moraschi
Stefania
S
Vallini
Ivan
I
Tardito
Daniela
D
Tiraboschi
Ettore
E
Musazzi
Laura
L
Giambelli
Roberto
R
Gennarelli
Massimo
M
Racagni
Giorgio
G
Barlati
Sergio
S
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D017393:RNA Editing / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000928:Antidepressive Agents; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors