The dopamine metabolite 3-methoxytyramine is a neuromodulator.
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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.
Cyclic AMP Response Element-Binding Protein
Extracellular Signal-Regulated MAP Kinases
Mice, Inbred C57BL
Published Version (Please cite this version)10.1371/journal.pone.0013452
Publication InfoSotnikova, 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.
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Associate Research Professor of Cell Biology
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
Assistant Professor of Psychiatry and Behavioral Sciences
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