Send to

Choose Destination
See comment in PubMed Commons below
Eur J Pharmacol. 2008 Feb 12;580(3):350-4. doi: 10.1016/j.ejphar.2007.11.028. Epub 2007 Nov 24.

Do selective serotonin reuptake inhibitors acutely increase frontal cortex levels of serotonin?

Author information

Depression and Anxiety Research, Discovery Neuroscience, Wyeth Research, Princeton, NJ 08543, USA.


Selective serotonin uptake inhibitors (SSRIs) exert their effects by inhibiting serotonin (5-HT) re-uptake. Although blockade occurs almost immediately, the neurochemical effects on 5-HT, as measured by in vivo microdialysis, have been a matter of considerable debate. In particular, literature reports yield conflicting neurochemical results in the rat frontal cortex. Thus, while some groups consistently find increases in extracellular 5-HT levels following acute SSRI administration, others reproducibly report an absence of these acute serotonergic effects. In an attempt to unravel this apparent discrepancy, we combined published literature with in-house microdialysis experiments. When we plotted the lateral stereotaxic coordinate of the dialysis probe against published reports on the acute effects of fluoxetine a clear correlation was revealed. Whereas pronounced increases in SSRI-induced 5-HT were observed when the dialysis probe was placed 0 to 1 mm from the midline, effects diminished when the lateral probe placement was greater than 3 mm from the midline. In-house microdialysis studies corroborated these reports. Overall, these results illustrate - for the first time - that the midline stereotaxic coordinate is critical for interpreting the acute serotonergic effects of SSRIs within the frontal cortex. Moreover, the common observation that the clinical efficacy of SSRIs is not evident following acute administration complements preclinical microdialysis results in the lateral frontal cortex. The significance of this observation, along with potential explanations for the disparate neurochemical findings in the medial versus lateral cortices, will be discussed.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center