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Published on: September 23, 2015
Antidepressant treatments change 5-HT2C receptor mRNA expression in rat prefrontal/frontal cortex and hippocampus
Alessandro Barbon1, Cesare Orlandi, Luca La Via
1Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies and National Institute of Neuroscience, University of Brescia, Brescia, Italy.
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.
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.
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.
Insights
Antidepressants alter serotonin 2C receptor mRNA expression in rat brains, with region-specific and time-dependent effects. RNA editing levels showed minimal changes, suggesting expression modulation is key.
Area of Science:
- Neuroscience
- Molecular Psychiatry
Background:
- The serotonin 2C receptor (5-HTR2C) is implicated in affective disorders and antidepressant action.
- Antidepressant treatments can modulate neurotransmitter receptor systems.
Purpose of the Study:
- To investigate the impact of chronic fluoxetine and reboxetine treatment on 5-HTR2C mRNA expression and RNA editing in rat prefrontal cortex and hippocampus.
- To determine the time course of these changes during treatment and withdrawal.
Main Methods:
- Chronic administration of fluoxetine and reboxetine to rats.
- Quantitative analysis of 5-HTR2C mRNA expression levels using RT-PCR.
- Assessment of 5-HTR2C RNA editing at specific sites (A, B, C, C', D).
Main Results:
- Both fluoxetine and reboxetine led to a significant down-regulation of 5-HTR2C mRNA in the prefrontal/frontal cortex, persisting after drug withdrawal.
- In the hippocampus, reboxetine caused down-regulation, while fluoxetine induced significant up-regulation of 5-HTR2C mRNA.
- No significant alterations in overall 5-HTR2C RNA editing frequency were observed, though minor decreases at C' and D sites were noted with reboxetine.
Conclusions:
- Chronic antidepressant treatment significantly influences 5-HTR2C mRNA expression in a brain area- and time-specific manner.
- RNA editing of the 5-HT2C receptor is only slightly affected by these antidepressant treatments.
- These findings highlight the complex regulation of 5-HTR2C by antidepressants, primarily at the mRNA expression level.
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