Back to Search Start Over

Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study.

Authors :
Selvaraj, S
Turkheimer, F
Rosso, L
Faulkner, P
Mouchlianitis, E
Roiser, J P
McGuire, P
Cowen, P J
Howes, O
Source :
Molecular Psychiatry; Dec2012, Vol. 17 Issue 12, p1254-1260, 7p, 1 Black and White Photograph, 1 Diagram, 1 Chart, 2 Graphs
Publication Year :
2012

Abstract

Serotonin (5-HT) neurotransmission is implicated in cognitive and emotional processes and a number of neuropsychiatric disorders. The use of positron emission tomography (PET) to measure ligand displacement has allowed estimation of endogenous dopamine release in the human brain; however, applying this methodology to assess central 5-HT release has proved more challenging. The aim of this study was to assess the sensitivity of a highly selective 5-HT<subscript>1A</subscript> partial agonist radioligand [<superscript>11</superscript>C]CUMI-101 to changes in endogenous 5-HT levels induced by an intravenous challenge with the selective 5-HT re-uptake inhibitor (SSRI), citalopram, in healthy human participants. We studied 15 healthy participants who underwent PET scanning in conjunction with [<superscript>11</superscript>C]CUMI-101 after receiving an intravenous infusion of citalopram 10 mg or placebo in a double-blind, crossover, randomized design. Regional estimates of binding potential (BP<subscript>ND</subscript>) were obtained by calculating total volumes of distribution (V<subscript>T</subscript>) for presynaptic dorsal raphe nucleus (DRN) and postsynaptic cortical regions. Relative to placebo, citalopram infusion significantly increased [<superscript>11</superscript>C]CUMI-101 BP<subscript>ND</subscript> at postsynaptic 5-HT<subscript>1A</subscript> receptors in several cortical regions, but there was no change in binding at 5-HT<subscript>1A</subscript> autoreceptors in the DRN. Across the postsynaptic brain regions, citalopram treatment induced a mean 7% in [<superscript>11</superscript>C]CUMI-101 BP<subscript>ND</subscript> (placebo 1.3 (0.2); citalopram 1.4 (0.2); paired t-test P=0.003). The observed increase in postsynaptic [<superscript>11</superscript>C]CUMI-101 availability identified following acute citalopram administration could be attributable to a decrease in endogenous 5-HT availability in cortical terminal regions, consistent with preclinical animal studies, in which acute administration of SSRIs decreases DRN cell firing through activation of 5-HT<subscript>1A</subscript> autoreceptors to reduce 5-HT levels in postsynaptic regions. We conclude that [<superscript>11</superscript>C]CUMI-101 may be sensitive to changes in endogenous 5-HT release in humans. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
13594184
Volume :
17
Issue :
12
Database :
Complementary Index
Journal :
Molecular Psychiatry
Publication Type :
Academic Journal
Accession number :
83493850
Full Text :
https://doi.org/10.1038/mp.2012.78