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Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain
Freyberg, Zachary Sonders, Mark S. Aguilar, Jenny I. Hiranita, Takato Karam, Caline S. Flores, Jorge Pizzo, Andrea B. Zhang, Yuchao Farino, Zachary J. Chen, Audrey
Freyberg, Zachary
Sonders, Mark S.
Aguilar, Jenny I.
Hiranita, Takato
Karam, Caline S.
Flores, Jorge
Pizzo, Andrea B.
Zhang, Yuchao
Farino, Zachary J.
Chen, Audrey
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Authors
Freyberg, Zachary
Sonders, Mark S.
Aguilar, Jenny I.
Hiranita, Takato
Karam, Caline S.
Flores, Jorge
Pizzo, Andrea B.
Zhang, Yuchao
Farino, Zachary J.
Chen, Audrey
Martin, Ciara A.
Kopajtic, Theresa A.
Fei, Hao
Hu, Gang
Lin, Yi-Ying
Mosharov, Eugene V.
McCabe, Brian D.
Freyberg, Robin
Wimalasena, Kandatege
Hsin, Ling-Wei
Sames, Dalibor
Krantz, David E.
Katz, Jonathan L.
Sulzer, David
Javitch, Jonathan A
Sonders, Mark S.
Aguilar, Jenny I.
Hiranita, Takato
Karam, Caline S.
Flores, Jorge
Pizzo, Andrea B.
Zhang, Yuchao
Farino, Zachary J.
Chen, Audrey
Martin, Ciara A.
Kopajtic, Theresa A.
Fei, Hao
Hu, Gang
Lin, Yi-Ying
Mosharov, Eugene V.
McCabe, Brian D.
Freyberg, Robin
Wimalasena, Kandatege
Hsin, Ling-Wei
Sames, Dalibor
Krantz, David E.
Katz, Jonathan L.
Sulzer, David
Javitch, Jonathan A
Other Names
Location
Time Period
Advisors
Original Date
Digitization Date
Issue Date
2016-02-16
Type
Article
Genre
Keywords
Vesicular monoamine transporter,Chromaffin granules,Neurotransmitter transporters,Secretory vesicles,Methamphetamine,Release,Neurons,Inhibition,Expression,Serotonin
Subjects (LCSH)
Citation
Freyberg, Z. et al. Mechanisms of amphetamine action
illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila
brain. Nat. Commun. 7:10652 doi: 10.1038/ncomms10652 (2016).
Abstract
Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT's role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H+ antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects.
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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Publisher
Nature Publishing Group
Journal
Book Title
Series
Nature Commubnications;vol.7:Article no.10652
Digital Collection
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Use and Reproduction
Open Access
Archival Collection
PubMed ID
DOI
ISSN
2041-1723