Dopamine pathway loss in nucleus accumbens and ventral tegmental area predicts apathetic behavior in MPTP-lesioned monkeys.

Experimental Neurology
C A BrownJoel S Perlmutter

Abstract

Apathy, primarily defined as a lack of motivation, commonly occurs in people with Parkinson disease (PD). Although dysfunction of basal ganglia pathways may contribute to apathy, the role of dopamine remains largely unknown. We investigated the role of dopaminergic pathways in the manifestation of apathetic behaviors by measuring the effects of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on monkeys' willingness to attempt goal directed behaviors, distinct from their ability to perform tasks. Fifteen macaques received variable doses of MPTP, had PET scans with [(11)C]-dihydrotetrabenazine (DTBZ), [(11)C]-2β-3β-4-fluorophenyltropane (CFT), and [(18)F]-fluorodopa (FD) and performed tasks to assess apathetic behaviors and motor impairment. At 8 weeks post-MPTP, primates were euthanized and stereological cell counts and dopamine measurements were done. Apathy scores were compared to motor scores, in vitro and in vivo dopaminergic measures. Apathy scores increased following MPTP and correlated with DTBZ (r(S) = -0.85), CFT (r(S) = -0.87), and FD (r(S) = -0.85) specific uptake in nucleus accumbens (NAcc,) and dopaminergic cell counts in ventral tegmental area (VTA, r(S) = -0.80). Dopaminer...Continue Reading

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Citations

Apr 4, 2014·Psychopharmacology·Michael A P BloomfieldOliver D Howes
May 23, 2014·Brain Research·LinLin TianJoel S Perlmutter
Aug 1, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Aude Gesquière-DandoAlexandre Eusebio
Oct 12, 2014·Brain Structure & Function·Véronique Sgambato-FaureLéon Tremblay
Sep 2, 2015·Neurobiology of Disease·M Angela CenciHanna S Lindgren
May 13, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Nicolas CarriereDavid Devos
Jul 22, 2014·Annals of Neurology·Laura L DuganJoel S Perlmutter
Apr 16, 2013·Pharmacology, Biochemistry, and Behavior·Mónica Méndez-DíazOscar Prospéro-García
Mar 15, 2015·Frontiers in Behavioral Neuroscience·Elodie DurandFranck Durif
Oct 3, 2014·Journal of Clinical and Experimental Neuropsychology·Rujvi KamatUNKNOWN TMARC Group
Jun 21, 2016·Psychiatry Research. Neuroimaging·Pietro De RossiGianfranco Spalletta
Jul 1, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Krista L LanctôtEleenor H Abraham
Jul 28, 2016·Brain : a Journal of Neurology·Kinan MuhammedMasud Husain
Dec 2, 2017·Brain : a Journal of Neurology·Mathias PessiglioneRaphaël Le Bouc
Apr 15, 2015·Journal of Parkinson's Disease·María SierraPaul Krack
Dec 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Michael E Goldberg
Apr 5, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Anna CastriotoPaul Krack
Feb 6, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Antonio P StrafellaUNKNOWN IPMDS-Neuroimaging Study Group
Aug 28, 2020·Frontiers in Neuroscience·Hai-Hua SunChun-Feng Liu
Feb 26, 2019·Frontiers in Molecular Neuroscience·Christelle LasbleizJean-Michel Verdier
Apr 16, 2021·Brain Communications·Kinan MuhammedMasud Husain
Jun 6, 2021·Scientific Reports·Kristen A McLaurinRosemarie M Booze

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