Role of extracellular serotonin levels
in the effect of 5-HT(1B) receptor blockade
by
De Groote L, Klompmakers AA, Olivier B, Westenberg HG.
Department of Psychiatry,
Rudolf Magnus Institute of Neuroscience,
University Medical Center Utrecht,
Heidelberglaan 100, 3584 CX,
Utrecht, The Netherlands.
Psychopharmacology (Berl). 2003 May;167(2):153-8. Epub 2003 Mar 18

ABSTRACT

The release of serotonin (5-HT) at serotonergic nerve terminals is regulated by 5-HT(1B) autoreceptors. Several studies have reported that the effects of selective 5-HT reuptake inhibitors (SSRIs) on extracellular 5-HT are augmented by 5-HT(1B) receptor antagonists, whereas administration of these antagonists alone do not enhance 5-HT levels. It has been suggested that 5-HT(1B) receptors have low basal endogenous activity and therefore elevated endogenous 5-HT levels are needed to elicit an effect of 5-HT(1B) receptor antagonists. To test this hypothesis, different strategies were used to enhance 5-HT levels in the rat frontal cortex to assess the effects of locally applied NAS-181, a new selective 5-HT(1B) receptor antagonist. Blockade of 5-HT(1B) receptors with NAS-181 dose dependently augmented 5-HT levels when 5-HT levels were enhanced by a SSRI. No additional effect of NAS-181 on 5-HT output was found when 5-HT levels were enhanced by KCl depolarization-induced release or by preventing degradation of 5-HT with the monoamine oxidase inhibitor pargyline. In the presence of fluvoxamine, the increased 5-HT release evoked by KCl depolarization was augmented by NAS-181, supporting the idea that blockade of 5-HT transporters is necessary to measure an effect of 5-HT(1B) receptor blockade. In conclusion, the results provide circumstantial evidence that the effect of a 5-HT(1B) receptor antagonist depends on extracellular 5-HT levels, but strongly suggest that additional 5-HT reuptake inhibition is required to detect any effect of 5-HT(1B) receptor antagonist on 5-HT levels by in vivo microdialysis.

P11
SSRIs
5-HT1
5-HT2
5-HT3
5-HT1a
5-HT2c
Anpirtoline
Eltoprazine
Zolmitriptan
Knockout mice
5-HT2c/5-HT2b
5-HT1a v 5-HT1b
SSRIs and 5-HT1b
MDMA and 5-HT1a
MDMA and 5-HT1b
5-HT1b and reward
5-HT1b and anxiety
Aggression and serotonin
5-HT-moduline, serotonin and mood
5-HT1b inverse agonists as antidepressants

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