The dopamine metabolite 3-methoxytyramine is a neuromodulator.
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.
Type
Journal articleSubject
AnimalsBehavior, Animal
Blotting, Western
Corpus Striatum
Cyclic AMP Response Element-Binding Protein
Dopamine
Extracellular Signal-Regulated MAP Kinases
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphorylation
Signal Transduction
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https://hdl.handle.net/10161/4579Published Version (Please cite this version)
10.1371/journal.pone.0013452Publication Info
Sotnikova, Tatyana D; Beaulieu, Jean-Martin; Espinoza, Stefano; Masri, Bernard; Zhang,
Xiaodong; Salahpour, Ali; ... Gainetdinov, Raul R (2010). The dopamine metabolite 3-methoxytyramine is a neuromodulator. PLoS One, 5(10). pp. e13452. 10.1371/journal.pone.0013452. Retrieved from https://hdl.handle.net/10161/4579.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Lawrence Simeon Barak
Associate Research Professor of Cell Biology
Marc G. Caron
James B. Duke Distinguished Professor of Cell Biology
Studies of the mechanisms of action and regulation of hormones and neurotransmitters
at the cellular and molecular levels constitute the main goals our of research activities.
G protein-coupled receptors (GPCR) mediate the actions of signaling molecules from
unicellular organisms to man. We have used adrenergic and dopamine receptors to characterize
the structure/function and regulation mechanisms of these prototypes of G protein-coupled
receptors. Another approach has been to characterize
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Xiaodong Zhang
Assistant Professor of Psychiatry and Behavioral Sciences
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