title: Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson's disease.
abstract: Parkinson's disease (PD) involves the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) that is thought to cause the classical motor symptoms of this disease. However, motivational and affective impairments are also often observed in PD patients. These are usually attributed to a psychological reaction to the general motor impairment and to a loss of some of the neurons within the ventral tegmental area (VTA). We induced selective lesions of the VTA and SNc DA neurons that did not provoke motor deficits, and showed that bilateral dopamine loss within the SNc, but not within the VTA, induces motivational deficits and affective impairments that mimicked the symptoms of PD patients. Thus, motivational and affective deficits are a core impairment of PD, as they stem from the loss of the major group of neurons that degenerates in this disease (DA SNc neurons) and are independent of motor deficits.
authors: 1] Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France [2] Université Joseph Fourier, Grenoble, France.
authors: G
authors: G
authors: Drui
authors: 1] Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France [2] Université Joseph Fourier, Grenoble, France.
authors: S
authors: S
authors: Carnicella
authors: 1] Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France [2] Université Joseph Fourier, Grenoble, France.
authors: C
authors: C
authors: Carcenac
authors: 1] Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France [2] Université Joseph Fourier, Grenoble, France.
authors: M
authors: M
authors: Favier
authors: 1] Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France [2] Université Joseph Fourier, Grenoble, France.
authors: A
authors: A
authors: Bertrand
authors: 1] Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France [2] Université Joseph Fourier, Grenoble, France.
authors: S
authors: S
authors: Boulet
authors: 1] Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France [2] Université Joseph Fourier, Grenoble, France [3] Centre Hospitalier Universitaire de Grenoble, Grenoble, France.
authors: M
authors: M
authors: Savasta
mesh_terms: D000339:Affect / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine / Q000008:administration & dosage; D010300:Parkinson Disease / Q000503:physiopathology* / Q000523:psychology*; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D016627:Oxidopamine; D004298:Dopamine
references: Nat Rev Neurol. 2011 Dec 26;8(1):35-47
references: 22198405
references: Trends Neurosci. 2004 Aug;27(8):468-74
references: 15271494
references: Parkinsons Dis. 2011;2011:987084
references: 21766003
references: Neuron. 2010 Dec 9;68(5):815-34
references: 21144997
references: Brain. 2008 May;131(Pt 5):1303-10
references: 18344560
references: Exp Neurol. 1998 Aug;152(2):259-77
references: 9710526
references: Prog Neurobiol. 1996 Jun;49(3):215-66
references: 8878304
references: J Psychiatr Pract. 2004 May;10(3):196-9
references: 15330228
references: Curr Opin Neurol. 2003 Dec;16 Suppl 2:S3-9
references: 15129844
references: Nat Neurosci. 2005 Apr;8(4):484-9
references: 15793577
references: Eur J Neurosci. 2012 Jun;35(12):1894-907
references: 22708601
references: J Neurosci. 1995 May;15(5 Pt 2):3863-75
references: 7751951
references: CNS Neurol Disord Drug Targets. 2006 Feb;5(1):25-43
references: 16613552
references: Neurosci Biobehav Rev. 2004 Jan;27(8):721-8
references: 15019422
references: J Neurosci. 2006 Oct 18;26(42):10768-76
references: 17050715
references: Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8114-9
references: 18541917
references: Behav Brain Res. 2009 Apr 12;199(1):89-102
references: 18950658
references: Cereb Cortex. 2006 Jul;16(7):916-28
references: 16207933
references: Brain. 1999 Aug;122 ( Pt 8):1437-48
references: 10430830
references: J Neurosci. 2003 Oct 15;23(28):9395-402
references: 14561867
references: N Engl J Med. 1988 Apr 7;318(14):876-80
references: 3352672
references: Brain. 2010 Apr;133(Pt 4):1111-27
references: 20237128
references: Eur J Neurol. 2010 Mar;17(3):364-76
references: 20050885
references: J Neuropsychiatry Clin Neurosci. 1991 Summer;3(3):243-54
references: 1821241
references: J Biol Chem. 2006 Feb 24;281(8):4931-7
references: 16306048
references: Lancet Neurol. 2009 May;8(5):464-74
references: 19375664
references: Br J Pharmacol. 1978 Jan;62(1):19-24
references: 563752
references: Brain Res. 2001 Mar 2;893(1-2):178-85
references: 11223005
references: Exp Neurol. 2012 Jul;236(1):190-7
references: 22579525
references: Eur J Neurosci. 2002 Apr;15(8):1363-70
references: 11994130
references: Science. 1961 Sep 29;134(3483):943-4
references: 13714876
references: Trends Neurosci. 2010 Oct;33(10):474-84
references: 20832128
references: Neuropsychopharmacology. 2011 Feb;36(3):569-79
references: 20980989
references: Brain Res Rev. 2007 Nov;56(1):27-78
references: 17574681
references: J Neurosci. 2010 Feb 10;30(6):2356-64
references: 20147561
references: Nat Rev Neurosci. 2006 Jun;7(6):464-76
references: 16715055
references: Mov Disord. 2008 May 15;23(7):964-969
references: 18398913
references: J Neurosci Methods. 1996 May;66(1):1-11
references: 8794935
references: Neuroscience. 2008 Oct 28;156(4):830-40
references: 18817851
references: Neurosci Biobehav Rev. 2004 Jul;28(4):415-31
references: 15289006
references: Trends Neurosci. 2009 Oct;32(10):517-24
references: 19758714
references: Trends Neurosci. 2007 May;30(5):194-202
references: 17408759
references: Ann N Y Acad Sci. 2008;1129:35-46
references: 18591467
references: Physiol Rev. 1991 Jan;71(1):155-234
references: 1986388
references: Eur J Neurol. 2011 Mar;18 Suppl 1:11-5
references: 21255198
references: Brain Res. 1984 Jun 15;303(2):319-29
references: 6430466