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Regulation of Dopamine Release by Striatal Acetylcholine and Nicotine Is via Distinct Nicotinic Acetylcholine Receptors in Dorsal vs. Ventral Striatum

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Book cover The Basal Ganglia IX

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 58))

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Abstract

Striatal dopamine (DA) neurotransmission plays a fundamental role in the reinforcing and ultimately addictive effects of nicotine. Both nicotine and endogenous acetylcholine (ACh) regulate striatal DA release via β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) on striatal axons. The subfamily of β2*-nAChRs responsible for these potent synaptic effects could offer a molecular target for therapeutic strategies in nicotine addiction. We explored the role of the α6β2*-nAChRs in the nucleus accumbens (NAc) and caudate-putamen (CPu) by observing action potential-dependent DA release from synapses in real time using fast-scan cyclic voltammetry at carbon-fibre microelectrodes in mouse striatal slices. We show that α6β2*-nAChRs dominate in the control of DA release by ACh and nicotine in NAc but have a more minor role in CPu alongside other β2*-nAChRs (e.g. α4*). These data offer new insights to suggest striatal α6*-nAChRs as a molecular target for a therapeutic strategy for nicotine addiction.

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Acknowledgements

The authors acknowledge support from the Parkinson’s Disease Society (UK), MJ Fox Foundation, the Biotechnology and Biological Sciences Research Council (UK), and Eli Lilly UK, the Paton Fellowship (University of Oxford).

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Authors and Affiliations

  1. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK

    Richard Exley, Michael A. Clements & Stephanie J. Cragg

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  1. Richard Exley
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  2. Michael A. Clements
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  3. Stephanie J. Cragg
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Corresponding author

Correspondence to Richard Exley .

Editor information

Editors and Affiliations

  1. Dept. Anatomy & Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, 1007 MB, Netherlands

    Hendrik Jan Groenewegen

  2. Medical Center, Vrije Universiteit, Van der Boechorststraat 7, Amsterdam, 1081 BT, Netherlands

    Pieter Voorn

  3. Department of Neurology, Vrije Universiteit Medical Center, De Boelelaan 1117, Amsterdam, 1081 HV, Netherlands

    Henk W. Berendse

  4. Medical Center, Vrije Universiteit, Van der Boechorststraat 7, Amsterdam, 1081 BT, Netherlands

    Antonius B. Mulder

  5. Medical Centre, Radboud University Nijmegen, Geert Grooteplein 21a, Nijmegen, 6525 EZ, Netherlands

    Alexander R. Cools

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Exley, R., Clements, M.A., Cragg, S.J. (2009). Regulation of Dopamine Release by Striatal Acetylcholine and Nicotine Is via Distinct Nicotinic Acetylcholine Receptors in Dorsal vs. Ventral Striatum. In: Groenewegen, H., Voorn, P., Berendse, H., Mulder, A., Cools, A. (eds) The Basal Ganglia IX. Advances in Behavioral Biology, vol 58. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0340-2_25

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  • DOI: https://doi.org/10.1007/978-1-4419-0340-2_25

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  • Online ISBN: 978-1-4419-0340-2

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