Endogenous nicotinic cholinergic activity regulates dopamine release in the striatum
Abstract
Dopamine is vital for coordinated motion and for association learning linked to behavioral reinforcement. Here we show that the precise overlap of striatal dopaminergic and cholinergic fibers underlies potent control of dopamine release by ongoing nicotinic receptor activity. In mouse striatal slices, nicotinic antagonists or depletion of endogenous acetylcholine decreased evoked dopamine release by 90%. Nicotine at the concentration experienced by smokers also regulated dopamine release. In mutant mice lacking the beta2 nicotinic subunit, evoked dopamine release was dramatically suppressed, and those mice did not show cholinergic regulation of dopamine release. The results offer new perspectives when considering nicotine addiction and the high prevalence of smoking in schizophrenics.
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nAChRs containing the β2 subunit are essential for nicotine to depolarize DA cell bodies in the VTA and increase their firing rate.
“Electrophysiological studies have shown that nAChRs containing the β2 subunit are essential for the ability of nicotine to depolarize DA cell bodies in the VTA and to increase their firing rate (Picciotto et al. 1998;Zhou et al. 2001).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Zhou et al. 2001
Cites
Schizophrenia, sensory gating, and nicotinic receptors
Adler, L. E., Olincy, A., Waldo, M., Harris, J. G., Griffith, J., Stevens, K., Flach, K., Nagamoto, H., Bickford, P., Leonard, S., et al. (1998) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a033320 · Cited by 690 · see citing works
Marshall, D. L., Redfern, P. H., & Wonnacott, S. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68041511.x · Cited by 284 · see citing works
The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence
Balfour, D. J. K., Wright, A. E., Benwell, M. E. M., & Birrell, C. E. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00202-3 · Cited by 231 · see citing works
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Dopamine-mediated regulation of corticostriatal synaptic plasticity
Calabresi, P., Picconi, B., Tozzi, A., & Di Filippo, M. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.001 · Cited by 865 · see citing works
Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum
Lovinger, D. M. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.01.008 · Cited by 488 · see citing works
It could be habit forming: drugs of abuse and striatal synaptic plasticity
Gerdeman, G. L., Partridge, J. G., Lupica, C. R., & Lovinger, D. M. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00065-1 · Cited by 480 · see citing works
Desensitization of neuronal nicotinic receptors
Quick, M. W., & Lester, R. A. J. (2002) · Journal of Neurobiology · doi:10.1002/neu.10109 · Cited by 456 · see citing works
Nicotine addiction and nicotinic receptors: lessons from genetically modified mice
Changeux, J.-P. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2849 · Cited by 453 · see citing works
PICCIOTTO, M., ADDY, N., MINEUR, Y., & BRUNZELL, D. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.12.005 · Cited by 451 · see citing works
Zoli, 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
Striatal 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
Nicotine addiction and comorbidity with alcohol abuse and mental illness
Dani, J. A., & Harris, R. A. (2005) · Nature Neuroscience · doi:10.1038/nn1580 · Cited by 382 · see citing works
Self-citationReward, addiction, withdrawal to nicotine
De Biasi, M., & Dani, J. A. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113734 · Cited by 366 · see citing works
“Although only ~2% of the striatal neurons are cholinergic, they have extremely dense axonal arbors that provide denser cholinergic innervation than is seen anywhere else in the brain (Butcher & Woolf 1984, Zhou et al. 2001, 2002).”
BackgroundMethodInfluentialSelf-citationWooltorton, 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
Self-citationFrequency-dependent modulation of dopamine release by nicotine
Zhang, H., & Sulzer, D. (2004) · Nature Neuroscience · doi:10.1038/nn1243 · Cited by 361 · see citing works
Nicotine as a modulator of behavior: beyond the inverted U
Picciotto, M. R. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00230-x · Cited by 257 · 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
Meaningful silences: how dopamine listens to the ACh pause
Cragg, S. J. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.01.003 · Cited by 245 · see citing works
The lipopolysaccharide Parkinson’s disease animal model: mechanistic studies and drug discovery
Dutta, G., Zhang, P., & Liu, B. (2008) · Fundamental & Clinical Pharmacology · doi:10.1111/j.1472-8206.2008.00616.x · Cited by 235 · see citing works
An action potential initiation mechanism in distal axons for the control of dopamine release
Liu, C., Cai, X., Ritzau-Jost, A., Kramer, P. F., Li, Y., Khaliq, Z. M., Hallermann, S., & Kaeser, P. S. (2022) · Science · doi:10.1126/science.abn0532 · Cited by 213 · see citing works
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
Self-citationRegulation of synaptic transmission and plasticity by neuronal nicotinic acetylcholine receptors
McKay, B. E., Placzek, A. N., & Dani, J. A. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.07.001 · Cited by 181 · see citing works
Self-citationControls of tonic and phasic dopamine transmission in the dorsal and ventral striatum
Zhang, L., Doyon, W. M., Clark, J. J., Phillips, P. E. M., & Dani, J. A. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.056317 · Cited by 161 · see citing works
Striatal cholinergic interneurons drive GABA release from dopamine terminals
Nelson, A. B., Hammack, N., Yang, C. F., Shah, N. M., Seal, R. P., & Kreitzer, A. C. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.023 · Cited by 169 · see citing works
Exley, R., Maubourguet, N., David, V., Eddine, R., Evrard, A., Pons, S., Marti, F., Threlfell, S., Cazala, P., McIntosh, J. M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103000108 · Cited by 159 · 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
Zhang, L., Dong, Y., Doyon, W. M., & Dani, J. A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.07.024 · Cited by 135 · see citing works
Self-citationMaskos, U. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.5 · Cited by 139 · see citing works
Fowler, C. D., Arends, M. A., & Kenny, P. J. (2008) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32830c360e · Cited by 131 · see citing works
Mansvelder, H. D., De Rover, M., McGehee, D. S., & Brussaard, A. B. (2003) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2003.08.099 · Cited by 130 · see citing works
Drenan, R. M., Grady, S. R., Steele, A. D., McKinney, S., Patzlaff, N. E., McIntosh, J. M., Marks, M. J., Miwa, J. M., & Lester, H. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2056-10.2010 · Cited by 127 · see citing works
Kramer, P. F., Brill-Weil, S. G., Cummins, A. C., Zhang, R., Camacho-Hernandez, G. A., Newman, A. H., Eldridge, M. A. G., Averbeck, B. B., & Khaliq, Z. M. (2022) · Neuron · doi:10.1016/j.neuron.2022.07.011 · Cited by 104 · see citing works
Perez, X. A., Bordia, T., McIntosh, J. M., Grady, S. R., & Quik, M. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.048843 · Cited by 77 · see citing works
Genetically encoded sensors for measuring histamine release both in vitro and in vivo
Dong, H., Li, M., Yan, Y., Qian, T., Lin, Y., Ma, X., Vischer, H. F., Liu, C., Li, G., Wang, H., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.02.024 · Cited by 67 · 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
Self-citationSynaptic and circuit functions of multitransmitter neurons in the mammalian brain
Wallace, M. L., & Sabatini, B. L. (2023) · Neuron · doi:10.1016/j.neuron.2023.06.003 · Cited by 59 · see citing works
Meyer, E. L., Yoshikami, D., & McIntosh, J. M. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05266.x · Cited by 58 · see citing works
Molecular and functional architecture of striatal dopamine release sites
Banerjee, A., Imig, C., Balakrishnan, K., Kershberg, L., Lipstein, N., Uronen, R.-L., Wang, J., Cai, X., Benseler, F., Rhee, J. S., et al. (2022) · Neuron · doi:10.1016/j.neuron.2021.10.028 · Cited by 58 · see citing works
Cholinergic Circuits and Signaling in the Pathophysiology of Schizophrenia
Berman, J. A., Talmage, D. A., & Role, L. W. (2007) · International Review of Neurobiology · doi:10.1016/s0074-7742(06)78007-2 · Cited by 47 · see citing works
Involvement of cholinergic neuronal systems in intravenous cocaine self-administration
Smith, J. E., Co, C., Yin, X., Sizemore, G. M., Liguori, A., Johnson, W. E., & Martin, T. J. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2003.11.002 · Cited by 47 · see citing works
Grilli, M., Patti, L., Robino, F., Zappettini, S., Raiteri, M., & Marchi, M. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05307.x · Cited by 40 · see citing works
Mesolimbic Dopamine and Habenulo-Interpeduncular Pathways in Nicotine Withdrawal
Dani, J. A., & De Biasi, M. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012138 · Cited by 34 · see citing works
Self-citationCoura, R. S., Cressant, A., Xia, J., de Chaumont, F., Olivo‐Marin, J. C., Pelloux, Y., Dalley, J. W., & Granon, S. (2013) · The FASEB Journal · doi:10.1096/fj.13-231084 · Cited by 33 · see citing works
Dong, Y., Zhang, T., Li, W., Doyon, W., & Dani, J. A. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-009-9231-6 · Cited by 23 · see citing works
Renda, A., Penty, N., Komal, P., & Nashmi, R. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.04.019 · Cited by 17 · see citing works
- Authors
- Zhou, F.-M., Liang, Y., & Dani, J. A.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Dani, John A.
- Venue
- Nature Neuroscience
- Published
- 2001-11-19
- Volume
- 4
- Issue
- 12
- Pages
- 1224-1229
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1557320868
- Cited by
- 585
- References
- 3
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 21 · 2023: 22 · 2022: 25 · 2021: 23 · 2020: 18 · 2019: 18 · 2018: 24 · 2017: 19 · 2016: 23 · 2015: 22 · 2014: 29 · 2013: 21 · 2012: 24
- FWCI
- 8.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA-12661, DA09411, R01DA009411, P01DA012661)
- National Institute of Neurological Disorders and Stroke (NS 21229)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- nicotinic acetylcholine receptors, dopamine release, striatum, cholinergic modulation, acetylcholine depletion, nicotine, nicotine dependence, schizophrenia
- MeSH terms
- Acetylcholine, Acetylcholinesterase, Action Potentials, Animals, Calcium, Choline O-Acetyltransferase, Cholinergic Fibers, Dopamine, Enzyme Inhibitors, Immunohistochemistry, Mice, Inbred C57BL, Synaptic Transmission, Neuromuscular Depolarizing Agents, Neurons, Nicotine, Receptors, Nicotinic, Smoking, Tetrodotoxin, Tyrosine 3-Monooxygenase, Neostriatum, Muscarinic Antagonists, Nicotinic Antagonists, Mice
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