Serotonin release measured in the human brain: a PET study with [11C]CIMBI-36 and d-amphetamine challenge

Autor: David J. Nutt, E.A. Rabiner, Yvonne Lewis, Mickael Huiban, David Erritzoe, Azeem Saleem, Sara Moz, Alessandro Colasanti, John Beaver, Graham E. Searle, Gitte M. Knudsen, Anne Lingford-Hughes, Oliver D. Howes, Samuel Turton, Jan Passchier, Roger N. Gunn, Abhishekh Hulegar Ashok
Rok vydání: 2019
Předmět:
Agonist
medicine.medical_specialty
INDUCED DOPAMINE RELEASE
TRANSMISSION
medicine.drug_class
FLUOXETINE
Endocrinology & Metabolism
03 medical and health sciences
chemistry.chemical_compound
POSITRON-EMISSION-TOMOGRAPHY
0302 clinical medicine
Dopamine
Internal medicine
BINDING
medicine
Radioligand
Pharmacology & Pharmacy
NEUROTRANSMITTER RELEASE
Neurotransmitter
Amphetamine
11 Medical and Health Sciences
Psychiatry
Pharmacology
Science & Technology
business.industry
Neurosciences
Binding potential
Hematology
Human brain
17 Psychology and Cognitive Sciences
030227 psychiatry
5-HT2A RECEPTOR
Psychiatry and Mental health
medicine.anatomical_structure
Endocrinology
chemistry
ENDOGENOUS OPIOID RELEASE
Neurosciences & Neurology
Serotonin
SENSITIVITY
business
Life Sciences & Biomedicine
SYSTEM
030217 neurology & neurosurgery
medicine.drug
Zdroj: Neuropsychopharmacology. 45:804-810
ISSN: 1740-634X
0893-133X
Popis: 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 hours after an oral dose of d-amphetamine (0.5 mg/kg). Dynamic PET data were acquired over 90 minutes, 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- (BPNDfrontalpost-dose/ BPNDfrontalbaseline) 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.
Databáze: OpenAIRE
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