Chronic phencyclidine administration reduces the expression and editing of specific glutamate receptors in rat prefrontal cortex.
Phencyclidine (PCP) induces a form of psychosis that mimics naturally occurring schizophrenia in the most relevant domains of the psychopathology. In this report, we investigated the effect of chronic treatment with PCP on expression and RNA editing of alpha-amino-propionic acid (AMPA) and kainate (KA) glutamate receptor (GluR), in the rat prefrontal cortex and the hippocampus. We found that chronic, but not acute, PCP treatment decreased GluRs expression in the rat prefrontal cortex but not in the hippocampus. In particular, the mRNA coding for GluR2 and GluR3 subunits were reduced by 50%, whereas those coding for KA GluR5 and GluR6 were decreased by 30%. In addition, we observed a decrease of the editing levels of the R/G site in the flop form of both GluR2 and GluR3 and a significant increase in the editing level of GluR6 Q/R site. The variation in the editing level of the R/G sites suggests that chronic PCP treatment induced the formation of glutamate receptor subunits with slower resensitization kinetics and, with respect to kainate receptors, an increase in the Q/R editing level might generate receptor channels with a lower permeability to cations. Combining all the data, it can be inferred that the PCP treatment induced a specific and site-selective reduction of glutamatergic neurotransmission in the prefrontal cortex but not in the hippocampus.
Barbon
Alessandro
A
Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Fumagalli
Fabio
F
La Via
Luca
L
Caracciolo
Luca
L
Racagni
Giorgio
G
Riva
Marco Andrea
MA
Barlati
Sergio
S
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D010622:Phencyclidine / Q000008:administration & dosage* / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism*; D017393:RNA Editing / Q000187:drug effects*; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics* / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism
D000243:Adenosine Deaminase; D018691:Excitatory Amino Acid Antagonists; D010622:Phencyclidine; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; C567955:ADARB1 protein, human