Prominent Role of α3/α6β2* nAChRs in Regulating Evoked Dopamine Release in Primate Putamen: Effect of Long-Term Nicotine Treatment
Open accessAbstract
Brain dopaminergic systems are critical in motor control as evidenced by findings that their disruption results in movement disorders such as Parkinson's disease. Nicotinic acetylcholine receptor (nAChR) activation plays an important role in regulating striatal dopaminergic function. Rodent studies show that short-term nicotine exposure influences stimulated striatal dopamine release with responsiveness dependent on neuronal activity. However, studies have not yet been done in nonhuman primates, nor has work been done to evaluate the effect of long-term nicotine exposure, which is relevant for therapies for chronic neurological disorders. Here, we used voltammetry to assess the role of nAChRs on evoked dopamine release from monkey putamen slices. In both ventral and dorsal putamen, alpha3/alpha6beta2(*) nAChRs regulated > or =80% of non-burst- (single pulse) nAChR-modulated dopamine release, and alpha4beta2(*) nAChRs regulated the remainder. Similar results were observed with burst-firing in ventral but not dorsal putamen, indicating that nAChR-modulated effects on release depend on the subregion and firing frequency. Next, we investigated the consequence of long-term nicotine exposure via the drinking water on nAChR-modulated responsiveness. Nicotine treatment altered both non-burst- and burst-stimulated dopamine release in ventral but not dorsal putamen. Altogether, these data support a predominant role for alpha3/alpha6beta2(*) nAChRs in the regulation of evoked dopamine release in nonhuman primate putamen. They also show that long-term nicotine treatment selectively modifies nAChR-modulated release in distinct striatal subregions. These findings have implications for the development of treatments for addiction and neurological disorders with nAChR dysfunction.
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The t90% measure of dopamine signal decay was not significantly different before and after chronic nicotine treatment.
“We found that this measure (t90%) was not significantly different before (control, 0.63 ± 0.44 s) and after chronic nicotine treatment (0.71 ± 0.36 s), which is consistent with the work of others (33).”
From Withdrawal from Chronic Nicotine Exposure Alters Dopamine Signaling Dynamics in the Nucleus Accumbens (2012) · cites this paper as [33]
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- Authors
- Perez, X. A., O’Leary, K. T., Parameswaran, N., McIntosh, J. M., & Quik, M.
- Affiliations
- Parkinson's Institute and Clinical Center (US)
- ORCID
- McIntosh, J. Michael
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 75
- Issue
- 4
- Pages
- 938-946
- ISSN
- 0026-895X (ISSN-L)
- PMC
- PMC2684934
- OpenAlex
- W2159943283
- Cited by
- 38
- References
- 41
- Citations by year
- 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 8 · 2012: 2
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tobacco-Related Disease Research Program (17RT-0119)
- National Institutes of Health (MH53631, GM 48677)
- National Institute of Mental Health (MH53631, R01MH053631)
- National Institute on Drug Abuse (R01DA012242, DA12242)
- National Institute of General Medical Sciences (P01GM048677, GM48677)
- National Institute of Neurological Disorders and Stroke (R01NS047162, NS42091, NS47162, R01NS042091)
- 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, alpha4beta2 nAChR, dopamine release, putamen, striatum, burst firing, non-human primates, Parkinson's disease, nicotine dependence
- MeSH terms
- Animals, Dopamine, Dose-Response Relationship, Drug, Female, Nicotine, Putamen, Receptors, Nicotinic, Saimiri, Time Factors
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