title: Antidepressant treatments change 5-HT2C receptor mRNA expression in rat prefrontal/frontal cortex and hippocampus.
abstract: OBJECTIVE
  Compelling evidence would suggest the involvement of the serotonin 2C receptor in the pathophysiology of affective disorders and in the action of antidepressants. We analyzed the time course of 5-HT2C receptor (5-HTR2C) mRNA expression during antidepressant treatment in the prefrontal/frontal cortex (P/FC) and in the hippocampus (HC) of rats chronically treated with fluoxetine (a selective serotonin reuptake inhibitor) and reboxetine (a selective noradrenaline reuptake inhibitor). We also analyzed the 5-HTR2C RNA-editing levels at the sites called A, B, C, C' and D, which are known to modulate 5-HTR2C receptor function.
  
  
  RESULTS
  The expression profile of 5-HTR2C mRNA was modified during treatment with both antidepressants. In particular, we found a general down-regulation of 5-HTR2C mRNA expression in P/FC, which became significant after 3 weeks of treatment with both antidepressants and persisted after a fourth week of drug withdrawal (-46% with fluoxetine, -41% with reboxetine, p < 0.05). In HC, however, reboxetine induced significant down-regulation (-56%, p < 0.05) of 5-HTR2C mRNA after 3 weeks, while fluoxetine induced threefold up-regulation (p < 0.01) by the 2nd and 3rd week, returning to the base level after drug withdrawal of both antidepressants. Moreover, the frequency of 5-HTR2C-edited isoforms showed no significant alterations, although analysis of the RNA-editing level at the single editing sites showed small decreases in the C' and D sites induced by reboxetine in P/FC.
  
  
  CONCLUSIONS
  Our results suggest that chronic administration of antidepressants in rats slightly modifies the editing levels of 5-HT2C receptor but has considerable influence on its mRNA expression patterns in a way that is area- and time-specific.
authors.affiliation: Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies and National Institute of Neuroscience, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barbon
authors.forename: Cesare
authors.initials: C
authors.lastname: Orlandi
authors.forename: Luca
authors.initials: L
authors.lastname: La Via
authors.forename: Luca
authors.initials: L
authors.lastname: Caracciolo
authors.forename: Daniela
authors.initials: D
authors.lastname: Tardito
authors.forename: Laura
authors.initials: L
authors.lastname: Musazzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mallei
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D017393:RNA Editing / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics* / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018759:Adrenergic Uptake Inhibitors; D005473:Fluoxetine; D009025:Morpholines; D000077593:Reboxetine; D044405:Receptor, Serotonin, 5-HT2C; D017367:Selective Serotonin Reuptake Inhibitors