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Effects of reduced endogenous 5‐HT on the in vivo binding of the serotonin transporter radioligand 11 C‐DASB in healthy humans
Author(s) -
Talbot Peter S.,
Frankle W. Gordon,
Hwang DahRen,
Huang Yiyun,
Suckow Raymond F.,
Slifstein Mark,
AbiDargham Anissa,
Laruelle Marc
Publication year - 2005
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20105
Subject(s) - serotonin transporter , serotonergic , chemistry , serotonin , binding potential , serotonin plasma membrane transport proteins , endocrinology , medicine , radioligand , raclopride , in vivo , dopamine , biochemistry , striatum , biology , receptor , microbiology and biotechnology
Although abnormal serotonin (5‐HT) function is implicated in a range of mental disorders, there is currently no method to directly assess 5‐HT synaptic levels in the living human brain. The in vivo binding of some dopamine (DA) radioligands such as 11 C‐raclopride is affected by fluctuations in endogenous DA, thus providing an indirect measure of DA presynaptic activity. Attempts to identify a serotonergic radiotracer with similar properties have proved unsuccessful. Here, we investigated in humans the effects of reduced synaptic 5‐HT on the in vivo binding of the 5‐HT transporter (SERT) radioligand 11 C‐DASB, using Positron Emission Tomography (PET) and the rapid tryptophan depletion (RTD) technique. Eight (8) subjects (5M, 3F) were scanned with 11 C‐DASB under control and reduced endogenous 5‐HT conditions, in a within‐subject, double‐blind, counterbalanced, crossover design. Regional distribution volumes (V T ) were calculated using kinetic modeling and metabolite‐corrected arterial input function. 11 C‐DASB specific binding was estimated as binding potential (BP) and specific to nonspecific equilibrium partition coefficient (V ′ 3 ), using the cerebellum as reference region. RTD caused small but significant mean reductions in 11 C‐DASB V T (−6.1%) and BP (−4.5%) across brain regions, probably explained by a concomitant reduction in 11 C‐DASB plasma free fraction (f 1 ) of similar magnitude. No significant change in 11 C‐DASB V ′ 3was observed between control and reduced 5‐HT conditions. Nor was there a significant relationship between the magnitude of tryptophan depletion and change in BP and V ′ 3across individual subjects. These results suggest that 11 C‐DASB in vivo binding is not affected by reductions in endogenous 5‐HT. Synapse 55:164–175, 2005. © 2004 Wiley‐Liss, Inc.