Show simple item record Sotnikova, TD Beaulieu, JM Espinoza, S Masri, B Zhang, X Salahpour, A Barak, LS Caron, MG Gainetdinov, RR
dc.coverage.spatial United States 2011-06-21T17:32:17Z 2010
dc.identifier.citation PLoS One, 2010, 5 (10), pp. e13452 - ?
dc.description.abstract Dopamine (3-hydroxytyramine) is a well-known catecholamine neurotransmitter involved in multiple physiological functions including movement control. Here we report that the major extracellular metabolite of dopamine, 3-methoxytyramine (3-MT), can induce behavioral effects in a dopamine-independent manner and these effects are partially mediated by the trace amine associated receptor 1 (TAAR1). Unbiased in vivo screening of putative trace amine receptor ligands for potential effects on the movement control revealed that 3-MT infused in the brain is able to induce a complex set of abnormal involuntary movements in mice acutely depleted of dopamine. In normal mice, the central administration of 3-MT caused a temporary mild hyperactivity with a concomitant set of abnormal movements. Furthermore, 3-MT induced significant ERK and CREB phosphorylation in the mouse striatum, signaling events generally related to PKA-mediated cAMP accumulation. In mice lacking TAAR1, both behavioral and signaling effects of 3-MT were partially attenuated, consistent with the ability of 3-MT to activate TAAR1 receptors and cause cAMP accumulation as well as ERK and CREB phosphorylation in cellular assays. Thus, 3-MT is not just an inactive metabolite of DA, but a novel neuromodulator that in certain situations may be involved in movement control. Further characterization of the physiological functions mediated by 3-MT may advance understanding of the pathophysiology and pharmacology of brain disorders involving abnormal dopaminergic transmission, such as Parkinson's disease, dyskinesia and schizophrenia.
dc.format.extent e13452 - ?
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0013452
dc.subject Animals
dc.subject Behavior, Animal
dc.subject Blotting, Western
dc.subject Corpus Striatum
dc.subject Cyclic AMP Response Element-Binding Protein
dc.subject Dopamine
dc.subject Extracellular Signal-Regulated MAP Kinases
dc.subject Humans
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Mice, Knockout
dc.subject Phosphorylation
dc.subject Signal Transduction
dc.title The dopamine metabolite 3-methoxytyramine is a neuromodulator.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-10-18 en_US
duke.description.endpage e13452 en_US
duke.description.issue 10 en_US
duke.description.startpage e13452 en_US
duke.description.volume 5 en_US
dc.relation.journal Plos One en_US
pubs.issue 10
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Duke Institute for Brain Sciences
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Cell Biology
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Neurobiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Cardiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Psychiatry & Behavioral Sciences
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Psychiatry & Behavioral Sciences/Psychiatry & Behavioral Sciences, Translational Neuroscience
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.publication-status Published online
pubs.volume 5
dc.identifier.eissn 1932-6203

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