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Changes in extracellular 5-HIAA concentrations as measured by in vivo microdialysis technique in relation to changes
Carina Stenfors1, Svante B Ross
1Bioscience, Local Discovery, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden. carina.stenfors@astrazeneca.com
Rationale:
The cerebral microdialysis technique has been widely used to monitor the release of 5-hydroxytryptamine (5-HT). The extracellular concentration of 5-HT has generally been shown to change after pharmacological manipulation as expected. Extracellular levels of the metabolite, 5-hydroxyindoleaceticacid (5-HIAA) does not always change in the same direction as 5-HT and has therefore generally been thought to be of no interest as a marker for 5-HT release.
Objective:
The aim of the present review is to analyse the connection between changes in extracellular levels of 5-HT and 5-HIAA evoked by various pharmacological means.
Methods:
Literature on in vivo microdialysis studies measuring extracellular 5-HT and 5-HIAA has been analysed with special attention to the great importance of the 5-HT re-uptake mechanism in determining their extracellular concentrations.
Results:
When the 5-HT reuptake mechanism is intact changes in extracellular levels of 5-HT and 5-HIAA go in the same directions, e.g decrease after compounds that decrease 5-HT release and increase after compounds that enhance 5-HT release. Because the extracellular 5-HIAA concentrations is 100-1000 times higher than that of 5-HT similar percentage changes imply that a very small part of the released 5-HT reaches the microdialysis probe under these conditions. When the 5-HT reuptake mechanism is blocked the extracellular 5-HT increases whereas extracellular 5-HIAA decreases mainly because of the 5-HT(1B) receptor-induced decrease in 5-HT release but in part also because of the inhibition of reuptake of 5-HT, both resulting in decreased formation of 5-HIAA.
Conclusion:
Drug-induced changes in extracellular 5-HIAA levels can give valuable information on the effects of these drugs on the 5-HT release.
