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dc.contributor.authorFreyberg, Zachary
dc.contributor.authorSonders, Mark S.
dc.contributor.authorAguilar, Jenny I.
dc.contributor.authorHiranita, Takato
dc.contributor.authorKaram, Caline S.
dc.contributor.authorFlores, Jorge
dc.contributor.authorPizzo, Andrea B.
dc.contributor.authorZhang, Yuchao
dc.contributor.authorFarino, Zachary J.
dc.contributor.authorChen, Audrey
dc.contributor.authorMartin, Ciara A.
dc.contributor.authorKopajtic, Theresa A.
dc.contributor.authorFei, Hao
dc.contributor.authorHu, Gang
dc.contributor.authorLin, Yi-Ying
dc.contributor.authorMosharov, Eugene V.
dc.contributor.authorMcCabe, Brian D.
dc.contributor.authorFreyberg, Robin
dc.contributor.authorWimalasena, Kandatege
dc.contributor.authorHsin, Ling-Wei
dc.contributor.authorSames, Dalibor
dc.contributor.authorKrantz, David E.
dc.contributor.authorKatz, Jonathan L.
dc.contributor.authorSulzer, David
dc.contributor.authorJavitch, Jonathan A
dc.date.accessioned2016-03-22T16:46:29Z
dc.date.available2016-03-22T16:46:29Z
dc.date.issued2016-02-16
dc.identifier.citationFreyberg, 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).en_US
dc.identifier.issn2041-1723
dc.identifier.otherWOS:000371021000004
dc.identifier.urihttp://dx.doi.org/10.1038/ncomms10652
dc.identifier.urihttp://hdl.handle.net/10057/11973
dc.descriptionThis 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/en_US
dc.description.abstractAmphetamines 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.en_US
dc.description.sponsorshipThis work was financially supported by K08 DA031241 (Z.F.), Louis V. Gerstner, Jr, Scholars Program (Z.F.), Leon Levy Foundation (Z.F.), NARSAD Young Investigator Award (C.S.K.), K05 DA022413, (J.A.J.), P01 DA12408 (J.A.J.), Lieber Center for Schizophrenia Research and Treatment award (J.A.J.), R01 DA007418 (D. Sulzer), PO1 DA0 10154 (D. Su.), JPB and Parkinson's Disease Foundations (D. Su.), R01 MH086545 (D. Sames), G. Harold & Leila Y. Mathers Charitable Foundation (D. Sa.), NS075572 (B.D.M.), AG08702 (B.D.M.), the Dana Foundation (B.D.M.), the Gatsby Initiative in Brain Circuitry (B.D.M.), New York Presbyterian Seizure Disorders Fund (B.D.M.), R01 MH076900 (D.E.K.), R01 ES015747 (D.E.K.), P01 ES016732 (D.E.K.), Brain and behaviour Research Foundation (D.E.K.), UCLA Brain Research Institute (D.E.K.), UCLA Molecular Toxicology Program, Ruth L. Kirschstein T32 ES015457 (C.A.M.), Ruth L. Kirschstein GM07185 (A.C.), R01 NS075222 (E.M.), and the Intramural Research Program of NIDA (J.L.K.).en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofseriesNature Commubnications;vol.7:Article no.10652
dc.rightsOpen Access
dc.subjectVesicular monoamine transporteren_US
dc.subjectChromaffin granulesen_US
dc.subjectNeurotransmitter transportersen_US
dc.subjectSecretory vesiclesen_US
dc.subjectMethamphetamineen_US
dc.subjectReleaseen_US
dc.subjectNeuronsen_US
dc.subjectInhibitionen_US
dc.subjectExpressionen_US
dc.subjectSerotoninen_US
dc.titleMechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brainen_US
dc.typeArticleen_US
dc.rights.holder© 2016 Macmillan Publishers Limited.en_US


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