Identification of the Nicotinic Receptor Subtypes Expressed on Dopaminergic Terminals in the Rat Striatum
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Neuronal nicotinic acetylcholine receptors (nAChRs) expressed on mesostriatal dopaminergic neurons are thought to mediate several behavioral effects of nicotine, including locomotion, habit learning, and reinforcement. Using immunoprecipitation and ligand-binding techniques, we have shown that both alpha6beta2* and alpha4(nonalpha6)beta2* nAChRs are expressed in the caudate-putamen and that only alpha6* nAChRs can bind alpha-conotoxin MII and methyllycaconitine with affinities of 1.3 and 40 nm, respectively. Further studies performed on 6-hydroxydopamine-lesioned striatum led to the identification of nAChR subtypes selectively expressed on dopaminergic terminals [alpha4alpha5beta2, alpha4alpha6beta2(beta3), and alpha6beta2(beta3)], nondopaminergic neuronal structures (alpha2alpha4beta2), or both structures (alpha4beta2). The identification of the nAChRs expressed on striatal dopaminergic terminals opens up the possibility of developing selective nAChR ligands active on dopaminergic systems and associated diseases, such as Parkinson's disease.
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DA neurons express heteromeric nAChRs containing α4, α5, α6, β2, and β3 subunits in various combinations, with predominant subtypes being α4/β2/α5 and α4/α6/β2/β3.
“DA neurons express heteromeric nAChRs containing the α4, α5, α6, β2, and β3 subunits in various combinations, with the predominant subtypes being α4/β2/α5 and α4/α6/ β2/β3.”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Zoli et al. 2002
The section on striatal receptor populations identifies α4, α5, α6, β2, and β3 in receptors on dopaminergic terminals. But it estimates four major populations: α4β2 and α4β2α5 at about 30% each, α6β2(β3) at about 25%, and α4α6β2(β3) at about 15%. Thus it does not support calling α4β2α5 and α4α6β2β3 the two predominant subtypes; β3 is also shown as optional in the latter composition. Page numbers were not provided in the passages. (LLM, conf=0.90)
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- Authors
- Zoli, M., Moretti, M., Zanardi, A., McIntosh, J. M., Clementi, F., & Gotti, C.
- Affiliations
- University of Milan (IT)
- University of Modena and Reggio Emilia (IT)
- University of Utah (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-10-15
- Volume
- 22
- Issue
- 20
- Pages
- 8785-8789
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6757689
- OpenAlex
- W2162000418
- Cited by
- 407
- References
- 28
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 11 · 2020: 10 · 2019: 13 · 2018: 15 · 2017: 9 · 2016: 16 · 2015: 13 · 2014: 16 · 2013: 10 · 2012: 14
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH53631, R01MH053631, R29MH053631)
- 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 › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotinic acetylcholine receptors, dopaminergic terminals, striatum, caudate-putamen, alpha4beta2 nAChR, alpha-conotoxin MII, methyllycaconitine, nicotine, 6-hydroxydopamine lesion, Parkinson's disease
- MeSH terms
- Animals, Binding, Competitive, Corpus Striatum, Dopamine, Ligands, Male, Precipitin Tests, Receptors, Nicotinic, Specific Pathogen-Free Organisms, Oxidopamine, Rats, Sprague-Dawley, Presynaptic Terminals, Nicotinic Agonists, Nicotinic Antagonists, Dopamine Uptake Inhibitors, Protein Subunits, Rats
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