Serotonin release measured in the human brain: a PET study with [11C]CIMBI-36 and d-amphetamine challenge
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Serotonin release measured in the human brain : a PET study with [11C]CIMBI-36 and d-amphetamine challenge. / Erritzoe, David; Ashok, Abhishekh H; Searle, Graham E; Colasanti, Alessandro; Turton, Samuel; Lewis, Yvonne; Huiban, Mickael; Moz, Sara; Passchier, Jan; Saleem, Azeem; Beaver, John; Lingford-Hughes, Anne; Nutt, David J; Howes, Oliver D; Gunn, Roger N; Knudsen, Gitte M; Rabiner, Eugenii A.
In: Neuropsychopharmacology, Vol. 45, No. 5, 2020, p. 804-810.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Serotonin release measured in the human brain
T2 - a PET study with [11C]CIMBI-36 and d-amphetamine challenge
AU - Erritzoe, David
AU - Ashok, Abhishekh H
AU - Searle, Graham E
AU - Colasanti, Alessandro
AU - Turton, Samuel
AU - Lewis, Yvonne
AU - Huiban, Mickael
AU - Moz, Sara
AU - Passchier, Jan
AU - Saleem, Azeem
AU - Beaver, John
AU - Lingford-Hughes, Anne
AU - Nutt, David J
AU - Howes, Oliver D
AU - Gunn, Roger N
AU - Knudsen, Gitte M
AU - Rabiner, Eugenii A
PY - 2020
Y1 - 2020
N2 - Positron emission tomography (PET) enables non-invasive estimation of neurotransmitter fluctuations in the living human brain. While these methods have been applied to dopamine and some other transmitters, estimation of 5-hydroxytryptamine (5-HT; Serotonin) release has proved to be challenging. Here we demonstrate the utility of the novel 5-HT2A receptor agonist radioligand, [11C]CIMBI-36, and a d-amphetamine challenge to evaluate synaptic 5-HT changes in the living human brain. Seventeen healthy male volunteers received [11C]CIMBI-36 PET scans before and 3 h after an oral dose of d-amphetamine (0.5 mg/kg). Dynamic PET data were acquired over 90 min, and the total volume of distribution (VT) in the frontal cortex and the cerebellum derived from a kinetic analysis using MA1. The frontal cortex binding potential (BPNDfrontal) was calculated as (VTfrontal/VTcerebellum) - 1. ∆BPNDfrontal = 1 - (BPNDfrontal post-dose/BPNDfrontal baseline) was used as an index of 5-HT release. Statistical inference was tested by means of a paired Students t-test evaluating a reduction in post-amphetamine [11C]CIMBI-36 BPNDfrontal. Following d-amphetamine administration, [11C]CIMBI-36 BPNDfrontal was reduced by 14 ± 13% (p = 0.002). Similar effects were observed in other cortical regions examined in an exploratory analysis. [11C]CIMBI-36 binding is sensitive to synaptic serotonin release in the human brain, and when combined with a d-amphetamine challenge, the evaluation of the human brain serotonin system in neuropsychiatric disorders, such as major depression and Parkinson's disease is enabled.
AB - Positron emission tomography (PET) enables non-invasive estimation of neurotransmitter fluctuations in the living human brain. While these methods have been applied to dopamine and some other transmitters, estimation of 5-hydroxytryptamine (5-HT; Serotonin) release has proved to be challenging. Here we demonstrate the utility of the novel 5-HT2A receptor agonist radioligand, [11C]CIMBI-36, and a d-amphetamine challenge to evaluate synaptic 5-HT changes in the living human brain. Seventeen healthy male volunteers received [11C]CIMBI-36 PET scans before and 3 h after an oral dose of d-amphetamine (0.5 mg/kg). Dynamic PET data were acquired over 90 min, and the total volume of distribution (VT) in the frontal cortex and the cerebellum derived from a kinetic analysis using MA1. The frontal cortex binding potential (BPNDfrontal) was calculated as (VTfrontal/VTcerebellum) - 1. ∆BPNDfrontal = 1 - (BPNDfrontal post-dose/BPNDfrontal baseline) was used as an index of 5-HT release. Statistical inference was tested by means of a paired Students t-test evaluating a reduction in post-amphetamine [11C]CIMBI-36 BPNDfrontal. Following d-amphetamine administration, [11C]CIMBI-36 BPNDfrontal was reduced by 14 ± 13% (p = 0.002). Similar effects were observed in other cortical regions examined in an exploratory analysis. [11C]CIMBI-36 binding is sensitive to synaptic serotonin release in the human brain, and when combined with a d-amphetamine challenge, the evaluation of the human brain serotonin system in neuropsychiatric disorders, such as major depression and Parkinson's disease is enabled.
U2 - 10.1038/s41386-019-0567-5
DO - 10.1038/s41386-019-0567-5
M3 - Journal article
C2 - 31715617
VL - 45
SP - 804
EP - 810
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 5
ER -
ID: 256325016