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Antidepressant treatments change 5-HT2C receptor mRNA expression in rat prefrontal/frontal cortex and hippocampus.
- Source :
-
Neuropsychobiology [Neuropsychobiology] 2011; Vol. 63 (3), pp. 160-8. Date of Electronic Publication: 2011 Jan 13. - Publication Year :
- 2011
-
Abstract
- Background/aims: 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.<br />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.<br />Conclusion: 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.<br /> (Copyright © 2011 S. Karger AG, Basel.)
- Subjects :
- Adrenergic Uptake Inhibitors pharmacology
Animals
Down-Regulation drug effects
Frontal Lobe metabolism
Hippocampus metabolism
Male
Prefrontal Cortex metabolism
RNA Editing drug effects
Rats
Rats, Sprague-Dawley
Reboxetine
Selective Serotonin Reuptake Inhibitors pharmacology
Time Factors
Up-Regulation drug effects
Fluoxetine pharmacology
Frontal Lobe drug effects
Hippocampus drug effects
Morpholines pharmacology
Prefrontal Cortex drug effects
Receptor, Serotonin, 5-HT2C genetics
Receptor, Serotonin, 5-HT2C metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0224
- Volume :
- 63
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuropsychobiology
- Publication Type :
- Academic Journal
- Accession number :
- 21228608
- Full Text :
- https://doi.org/10.1159/000321593