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

• Published in: European journal of pharmacology Vol. 580; no. 3; pp. 350 - 354
• Main Authors: Beyer, Chad E., Cremers, Thomas I.F.H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 12.02.2008; Elsevier
• Subjects: Animals; Antidepressants; Biological and medical sciences; Chromatography, High Pressure Liquid; Drug Synergism; Fluoxetine; Fluoxetine - administration & dosage; Fluoxetine - pharmacology; Injections, Subcutaneous; Male; Medical sciences; Microdialysis; Microdialysis - methods; Pharmacology. Drug treatments; Piperazines - administration & dosage; Piperazines - pharmacology; Prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Pyridines - administration & dosage; Pyridines - pharmacology; Rat; Rats; Rats, Sprague-Dawley; Review Literature as Topic; Serotonin; Serotonin - metabolism; Serotonin Antagonists - administration & dosage; Serotonin Antagonists - pharmacology; Serotonin Uptake Inhibitors - pharmacology; SSRI; SSRI; Microdialysis; Serotonin; Rat; Antidepressants; Fluoxetine; Prefrontal cortex; Psychotropic; Rodentia; Central nervous system; Frontal cortex; Reuptake inhibitor; Encephalon; Selective serotonin reuptake inhibitor; Vertebrata; Mammalia; Animal; Neurotransmitter; Antidepressant agent
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2007.11.028

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.