Neuronal Nicotinic Receptor a6 Subunit mRNA is Selectively Concentrated in Catecholaminergic Nuclei of the Rat Brain
Open accessAbstract
Although the neuronal nicotinic receptor a6 subunit was cloned several years ago, its functional significance remains to be investigated. Here we describe an in situ hybridization study of the mRNA for this subunit in the adult rat central nervous system using oligonucleotide probes. Specific a6 mRNA labelling was restricted to a few nuclei throughout the brain; it was particularly high in several catecholaminergic nuclei [the locus coeruleus (A6), the ventral tegmental area (A10) and the substantia nigra (A9)] at levels significantly higher than those found for any other known nicotinic receptor subunit mRNA. Labelling for a6 mRNA was also detected at lower levels in the reticular thalamic nucleus, the supramammillary nucleus and the mesencephalic V nucleus. Some cells of the medial habenula (medioventral part) and of the interpeduncular nucleus (central and lateral parts) were also labelled. The distribution of a6 mRNA was compared with the distribution of the other known nicotinic acetylcholine receptor subunit mRNAs. In several nuclei, the expression of a6 was complementary to those of other a subunits. Moreover, some of the cell groups (such as the substantia nigra, the ventral tegmental area and the locus coeruleus) previously thought to contain mainly a3 mRNA in fact were found to contain high levels of α6 mRNA. Finally, we found extensive colocalization of α6 and p3, indicating the possible existence of nicotinic receptor hetero‐oligomers containing both subunits. The present results show that a6 is the major nicotinic acetylcholine receptor a subunit expressed in dopaminergic cell groups of the mesencephalon and noradrenergic cells of the locus coeruleus. This suggests the involvement of the a6 subunit in some of the major functions of central nicotinic circuits, including the modulation of locomotor behaviour and reward.
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The α6 subunit appears to be selectively expressed in DA neurons.
“The α6 subunit appears to be selectively expressed in DA neurons (Le Novere et al. 1996;Drenan et al. 2008b)”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Le Novere et al. 1996
The title in our indexed copy says α6 subunit mRNA is selectively concentrated in catecholaminergic nuclei of the rat brain. The available passages do not specifically identify DA neurons or establish selective expression in them; they support the broader localization claim only. (LLM, conf=0.78)
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Cellular and molecular mechanisms of drug dependence
Koob, G. F., & Bloom, F. E. (1988) · Science · doi:10.1126/science.2903550 · Cited by 2,070 · see citing works
Flores, C. M., Rogers, S. W., Pabreza, L. A., Wolfe, B. B., & Kellar, K. J. (1992) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)08832-7 · Cited by 880 · see citing works
Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain
Picciotto, M. R., Zoli, M., Léna, C., Bessis, A., Lallemand, Y., LeNovère, N., Vincent, P., Pich, E. M., Brûlet, P., & Changeux, J.-P. (1995) · Nature · doi:10.1038/374065a0 · Cited by 668 · see citing works
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Picciotto, M. R., Zoli, M., Rimondini, R., Léna, C., Marubio, L. M., Pich, E. M., Fuxe, K., & Changeux, J.-P. (1998) · Nature · doi:10.1038/34413 · Cited by 1,320 · see citing works
Self-citationKoob, G. F., Sanna, P. P., & Bloom, F. E. (1998) · Neuron · doi:10.1016/s0896-6273(00)80557-7 · Cited by 1,026 · see citing works
Brain nicotinic acetylcholine receptors: native subtypes and their relevance
Gotti, C., Zoli, M., & Clementi, F. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.07.004 · Cited by 882 · see citing works
Self-citationThe dynamic effects of nicotine on the developing brain
Dwyer, J. B., McQuown, S. C., & Leslie, F. M. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.02.003 · Cited by 559 · see citing works
Effect of nicotine and nicotinic receptors on anxiety and depression
Picciotto, M. R., Brunzell, D. H., & Caldarone, B. J. (2002) · Neuroreport · doi:10.1097/00001756-200207020-00006 · Cited by 483 · see citing works
Structural and functional diversity of native brain neuronal nicotinic receptors
Gotti, C., Clementi, F., Fornari, A., Gaimarri, A., Guiducci, S., Manfredi, I., Moretti, M., Pedrazzi, P., Pucci, L., & Zoli, M. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.05.024 · Cited by 469 · see citing works
Self-citationZoli, M., Moretti, M., Zanardi, A., McIntosh, J. M., Clementi, F., & Gotti, C. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08785.2002 · Cited by 407 · see citing works
Self-citationStriatal dopamine neurotransmission: Regulation of release and uptake
Sulzer, D., Cragg, S. J., & Rice, M. E. (2016) · Basal Ganglia · doi:10.1016/j.baga.2016.02.001 · Cited by 382 · see citing works
Wooltorton, J. R. A., Pidoplichko, V. I., Broide, R. S., & Dani, J. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03176.2003 · Cited by 363 · see citing works
Nicotinic receptors in the brain. Links between molecular biology and behavior
Picciotto, M. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00146-3 · Cited by 354 · see citing works
Brain nicotinic receptors: structure and regulation, role in learning and reinforcement
Changeux, J.-P., Bertrand, D., Corringer, P.-J., Dehaene, S., Edelstein, S., Léna, C., Le Novère, N., Marubio, L., Picciotto, M., & Zoli, M. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00040-4 · Cited by 322 · see citing works
Self-citationPons, S., Fattore, L., Cossu, G., Tolu, S., Porcu, E., McIntosh, J. M., Changeux, J. P., Maskos, U., & Fratta, W. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3918-08.2008 · Cited by 312 · see citing works
Self-citationDiversity of native nicotinic receptor subtypes in mammalian brain
Zoli, M., Pistillo, F., & Gotti, C. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.11.003 · Cited by 277 · see citing works
Self-citationHeterogeneity and complexity of native brain nicotinic receptors
Gotti, C., Moretti, M., Gaimarri, A., Zanardi, A., Clementi, F., & Zoli, M. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.05.023 · Cited by 282 · see citing works
Self-citationForster, G. L., & Blaha, C. D. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00250.x · Cited by 271 · see citing works
Nicotine addiction: the possible role of functional upregulation
Buisson, B., & Bertrand, D. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01979-9 · Cited by 254 · see citing works
The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum
Grady, S. R., Salminen, O., Laverty, D. C., Whiteaker, P., McIntosh, J. M., Collins, A. C., & Marks, M. J. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.07.032 · Cited by 252 · see citing works
Exley, R., Clements, M. A., Hartung, H., McIntosh, J. M., & Cragg, S. J. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301617 · Cited by 242 · see citing works
Marubio, L. M., Gardier, A. M., Durier, S., David, D., Klink, R., Arroyo‐Jimenez, M. M., McIntosh, J. M., Rossi, F., Champtiaux, N., Zoli, M., et al. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02564.x · Cited by 242 · see citing works
Self-citationGotti, C., Guiducci, S., Tedesco, V., Corbioli, S., Zanetti, L., Moretti, M., Zanardi, A., Rimondini, R., Mugnaini, M., Clementi, F., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5095-09.2010 · Cited by 226 · see citing works
Self-citationGrady, S. R., Moretti, M., Zoli, M., Marks, M. J., Zanardi, A., Pucci, L., Clementi, F., & Gotti, C. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5121-08.2009 · Cited by 222 · see citing works
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Drenan, R. M., Grady, S. R., Whiteaker, P., McClure-Begley, T., McKinney, S., Miwa, J. M., Bupp, S., Heintz, N., McIntosh, J. M., Bencherif, M., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.009 · Cited by 197 · see citing works
Pidoplichko, V. I., Noguchi, J., Areola, O. O., Liang, Y., Peterson, J., Zhang, T., & Dani, J. A. (2004) · Learning & Memory · doi:10.1101/lm.70004 · Cited by 196 · see citing works
Nicotinic receptors in human brain: topography and pathology
Court, J. A., Martin-Ruiz, C., Graham, A., & Perry, E. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00110-1 · Cited by 180 · see citing works
Mechanisms of Nicotine Addiction
Picciotto, M. R., & Kenny, P. J. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a039610 · Cited by 157 · see citing works
Grady, S. R., Meinerz, N. M., Cao, J., Reynolds, A. M., Picciotto, M. R., Changeux, J., McIntosh, J. M., Marks, M. J., & Collins, A. C. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00019.x · Cited by 156 · see citing works
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Han, Z., Le Novère, N., Zoli, M., Hill, J. A., Champtiaux, N., & Changeux, J. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00262.x · Cited by 156 · see citing works
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Antolin-Fontes, B., Ables, J. L., Görlich, A., & Ibañez-Tallon, I. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.11.019 · Cited by 154 · see citing works
Nicotine and Parkinson's disease: implications for therapy
Quik, M., O'Leary, K., & Tanner, C. M. (2008) · Movement Disorders · doi:10.1002/mds.21900 · Cited by 154 · see citing works
Nguyen, H. N., Rasmussen, B. A., & Perry, D. C. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.056408 · Cited by 148 · see citing works
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Jackson, K. J., McIntosh, J. M., Brunzell, D. H., Sanjakdar, S. S., & Damaj, M. I. (2009) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.155457 · Cited by 135 · see citing works
Ferrari, R., Le Novère, N., Picciotto, M. R., Changeux, J. P., & Zoli, M. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2001.02009.x · Cited by 132 · see citing works
Self-citationFowler, C. D., Arends, M. A., & Kenny, P. J. (2008) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32830c360e · Cited by 131 · see citing works
Doura, M. B., Gold, A. B., Keller, A. B., & Perry, D. C. (2008) · Brain Research · doi:10.1016/j.brainres.2008.03.056 · Cited by 129 · see citing works
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Picciotto, M. R. (1998) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(98)00074-x · Cited by 117 · see citing works
Arroyo-Jiménez, M. D. M., Bourgeois, J.-P., Marubio, L. M., Le Sourd, A.-M., Ottersen, O. P., Rinvik, E., Fairén, A., & Changeux, J.-P. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-15-06475.1999 · Cited by 110 · see citing works
Self-citationPerry, D. C., Mao, D., Gold, A. B., McIntosh, J. M., Pezzullo, J. C., & Kellar, K. J. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.121228 · Cited by 106 · see citing works
Brunzell, D. H., Boschen, K. E., Hendrick, E. S., Beardsley, P. M., & McIntosh, J. M. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.171 · Cited by 95 · see citing works
Mugnaini, M., Tessari, M., Tarter, G., Merlo Pich, E., Chiamulera, C., & Bunnemann, B. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02220.x · Cited by 88 · see citing works
David, V., Besson, M., Changeux, J.-P., Granon, S., & Cazala, P. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.02.003 · Cited by 87 · see citing works
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Walsh, H., Govind, A. P., Mastro, R., Hoda, J. C., Bertrand, D., Vallejo, Y., & Green, W. N. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m703432200 · Cited by 87 · see citing works
Nicotine and endogenous opioids: neurochemical and pharmacological evidence
Hadjiconstantinou, M., & Neff, N. H. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.11.010 · Cited by 81 · see citing works
Nicotine exploits a COPI-mediated process for chaperone-mediated up-regulation of its receptors
Henderson, B. J., Srinivasan, R., Nichols, W. A., Dilworth, C. N., Gutierrez, D. F., Mackey, E. D. W., McKinney, S., Drenan, R. M., Richards, C. I., & Lester, H. A. (2014) · Journal of General Physiology · doi:10.1085/jgp.201311102 · Cited by 78 · see citing works
Age dependent nicotinic influences over dopamine neuron synaptic plasticity
Placzek, A. N., Zhang, T. A., & Dani, J. A. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.05.014 · Cited by 61 · see citing works
Nicotinic modulation of glutamatergic synaptic transmission in region CA3 of the hippocampus
Giocomo, L. M., & Hasselmo, M. E. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04316.x · Cited by 52 · see citing works
Cotinine selectively activates a subpopulation of α3/α6β2* nicotinic receptors in monkey striatum
O’Leary, K., Parameswaran, N., McIntosh, J. M., & Quik, M. (2008) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.136838 · Cited by 45 · see citing works
O'Leary, K. T., & Leslie, F. M. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01575.x · Cited by 42 · see citing works
Reuben, M., Boye, S., & Clarke, P. B. S. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00004-2 · Cited by 33 · see citing works
Champtiaux, N., Kalivas, P. W., & Bardo, M. T. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.10.017 · Cited by 33 · see citing works
Moen, J. K., & Lee, A. M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.745783 · Cited by 30 · see citing works
Visanji, N. P., Mitchell, S. N., O'Neill, M. J., & Duty, S. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.07.013 · Cited by 25 · see citing works
- Authors
- Le Novere, N., Zoli, M., & Changeux, J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Changeux, Jean‐Pierre
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 1996-11
- Volume
- 8
- Issue
- 11
- Pages
- 2428-2439
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2008579253
- Cited by
- 385
- References
- 3
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 8 · 2015: 7 · 2014: 15 · 2013: 6 · 2012: 11
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- Centre National de la Recherche Scientifique
- 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, alpha6 subunit, mRNA distribution, locus coeruleus, ventral tegmental area, substantia nigra, dopaminergic neurons, reward, locomotor behaviour
- MeSH terms
- Animals, Autoradiography, Base Sequence, Brain, Deoxyadenine Nucleotides, Molecular Sequence Data, Neurons, Organ Specificity, Receptors, Nicotinic, RNA, Messenger, Substantia Nigra, Sulfur Radioisotopes, Tegmentum Mesencephali, Transcription, Genetic, Tyrosine 3-Monooxygenase, Oligonucleotide Probes, Rats, Sprague-Dawley, In Situ Hybridization, Rats
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