title: A concurrent excitation and inhibition of dopaminergic subpopulations in response to nicotine.
abstract: Midbrain dopamine (DA) neurons are key players in motivation and reward processing. Increased DA release is thought to be central in the initiation of drug addiction. Whereas dopamine neurons are generally considered to be activated by drugs such as nicotine, we report here that nicotine not only induces excitation of ventral tegmental area (VTA) DA cells but also induces inhibition of a subset of VTA DA neurons that are anatomically segregated in the medial part of the VTA. These opposite responses do not correlate with the inhibition and excitation induced by noxious stimuli. We show that this inhibition requires D2 receptor (D2-R) activation, suggesting that a dopaminergic release is involved in the mechanism. Our findings suggest a principle of concurrent excitation and inhibition of VTA DA cells in response to nicotine. It promotes unexplored roles for DA release in addiction contrasting with the classical views of reinforcement and motivation, and give rise to a new interpretation of the mode of operation of the reward system.
authors: Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005 Paris, France.
authors: Raphaël
authors: R
authors: Eddine
authors: Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005 Paris, France.
authors: Sebastien
authors: S
authors: Valverde
authors: Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005 Paris, France.
authors: Stefania
authors: S
authors: Tolu
authors: Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005 Paris, France.
authors: Daniel
authors: D
authors: Dautan
authors: Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005 Paris, France.
authors: Audrey
authors: A
authors: Hay
authors: Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005 Paris, France.
authors: Carole
authors: C
authors: Morel
authors: Dynamics and Pathophysiology of Neuronal Networks, Center for Interdisciplinary Research in Biology, INSERM U667, College de France, 75005 Paris, France.
authors: Yihui
authors: Y
authors: Cui
authors: Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005 Paris, France.
authors: Bertrand
authors: B
authors: Lambolez
authors: Dynamics and Pathophysiology of Neuronal Networks, Center for Interdisciplinary Research in Biology, INSERM U667, College de France, 75005 Paris, France.
authors: Laurent
authors: L
authors: Venance
authors: Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005 Paris, France.
authors: Fabio
authors: F
authors: Marti
authors: Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005 Paris, France.
authors: Philippe
authors: P
authors: Faure
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000633:toxicity*; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D017448:Receptors, Dopamine D2; D009538:Nicotine
references: Mol Pharmacol. 2012 Apr;81(4):541-8
references: 22222765
references: Neuropharmacology. 2014 Jan;76 Pt B:351-9
references: 23578393
references: Neuron. 2004 Jun 24;42(6):939-46
references: 15207238
references: Nat Neurosci. 2014 Nov;17(11):1543-51
references: 25242304
references: Neuropsychopharmacology. 2011 Apr;36(5):1021-32
references: 21289604
references: Brain Struct Funct. 2013 Sep;218(5):1159-76
references: 22926514
references: Neuropsychopharmacology. 2011 Oct;36(11):2244-57
references: 21716264
references: Neuron. 2002 Mar 14;33(6):905-19
references: 11906697
references: Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4894-9
references: 19261850
references: Science. 2004 Mar 26;303(5666):2040-2
references: 15044807
references: J Neurosci. 2010 May 19;30(20):6975-83
references: 20484639
references: J Neurosci. 2009 Oct 21;29(42):13344-52
references: 19846722
references: Acta Physiol Scand. 1986 Nov;128(3):351-8
references: 3788613
references: Brain Struct Funct. 2012 Apr;217(2):591-612
references: 21935672
references: J Neurosci. 2012 Oct 24;32(43):15076-85
references: 23100428
references: Neuron. 2008 Mar 13;57(5):760-73
references: 18341995
references: Neuroscience. 2014 Dec 12;282:60-8
references: 24875175
references: Biochem Pharmacol. 2011 Oct 15;82(8):977-83
references: 21684263
references: Neuroscience. 2014 Dec 12;282:13-22
references: 24463000
references: Mol Psychiatry. 2014 Aug;19(8):930-6
references: 24296975
references: Neuron. 2011 Jun 9;70(5):855-62
references: 21658580
references: J Neurosci Methods. 1996 Apr;65(2):113-36
references: 8740589
references: J Neurosci. 2009 Mar 4;29(9):2915-25
references: 19261887
references: Neuroscience. 1984 May;12(1):1-16
references: 6462443
references: Neuroscience. 2014 Dec 12;282:86-100
references: 24881574
references: Mol Psychiatry. 2003 Jan;8(1):50-9, 9
references: 12556908
references: Nature. 2005 Jul 7;436(7047):103-7
references: 16001069
references: Psychopharmacology (Berl). 1996 Apr;124(4):293-9
references: 8739543
references: Trends Neurosci. 2012 Jul;35(7):422-30
references: 22459161
references: Neuroscience. 2008 Apr 9;152(4):1024-31
references: 18355970
references: J Neurosci. 2011 Jun 8;31(23):8476-90
references: 21653852
references: PLoS One. 2010;5(12):e15222
references: 21151605
references: Neuron. 2010 Dec 9;68(5):815-34
references: 21144997
references: Nature. 1998 Jan 8;391(6663):173-7
references: 9428762
references: Neuron. 2006 Jun 15;50(6):911-21
references: 16772172
references: Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8
references: 2899326
references: Mol Psychiatry. 2013 Mar;18(3):382-93
references: 22751493
references: J Neurosci. 2008 Sep 3;28(36):8908-13
references: 18768684
references: Synapse. 2002 Mar 15;43(4):227-37
references: 11835517