Imaging changes in synaptic acetylcholine availability in living human subjects
Open accessAbstract
UNLABELLED: In vivo estimation of β(2)-nicotinic acetylcholine receptor availability with molecular neuroimaging is complicated by competition between the endogenous neurotransmitter acetylcholine and the radioligand (123)I-3-[2(S)-2-azetidinylmethoxy]pyridine ((123)I-5-IA). We examined whether binding of (123)I-5-IA is sensitive to increases in extracellular levels of acetylcholine in humans, as suggested in nonhuman primates. METHODS: Six healthy subjects (31 ± 4 y) participated in a (123)I-5-IA SPECT study. After baseline scans, physostigmine (1-1.5 mg) was administered intravenously over 60 min, and 9 additional scans were obtained. RESULTS: We observed a significant reduction in the total volume of distribution after physostigmine administration (29% ± 17% in the cortex, 19% ± 15% in the thalamus, 19% ± 15% in the striatum, and 36% ± 30% in the cerebellum; P < 0.05). This reduction reflected a combination of a region-specific 7%-16% decrease in tissue concentration of tracer and a 9% increase in plasma parent concentration. CONCLUSION: These data suggest that increases in acetylcholine compete with (123)I-5-IA for binding to β(2)-nicotinic acetylcholine receptor. Additional validation of this paradigm is warranted, but it may be used to interrogate changes in extracellular acetylcholine.
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A higher level of acetylcholine competing for receptor binding was the likely reason for the decrease in nAChR availability.
“Post-mortem studies confirmed that a higher level of acetylcholine competing for receptor binding was the likely reason for the decrease in nAChR availability, and this has been confirmed in studies using a cholinesterase antagonist to increase acetylcholine levels dynamically (Esterlis et al., 2013).”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Esterlis et al., 2013
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- Authors
- Esterlis, I., Hannestad, J. O., Bois, F., Sewell, R. A., Tyndale, R. F., Seibyl, J. P., Picciotto, M. R., Laruelle, M., Carson, R. E., & Cosgrove, K. P.
- Affiliations
- Yale University (US)
- Centre for Addiction and Mental Health (CA)
- Institute for Neurodegenerative Disorders (US)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2012-11-15
- Volume
- 54
- Issue
- 1
- Pages
- 78-82
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC3703589
- OpenAlex
- W2138445726
- Cited by
- 38
- References
- 21
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 3
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- National Institute of Mental Health (K01MH092681, R01MH077681)
- National Institute on Drug Abuse (K01DA020651, K12DA000167)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Keywords
- physostigmine, volume of distribution, extracellular acetylcholine, SPECT imaging, human brain
- MeSH terms
- Acetylcholine, Adult, Azetidines, Brain, Extracellular Space, Female, Humans, Male, Physostigmine, Pyridines, Synapses, Tomography, Emission-Computed, Single-Photon
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