PMID- 26879809
OWN - NLM
STAT- MEDLINE
DCOM- 20160628
LR  - 20181113
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 7
DP  - 2016 Feb 16
TI  - Mechanisms of amphetamine action illuminated through optical monitoring of 
      dopamine synaptic vesicles in Drosophila brain.
PG  - 10652
LID - 10.1038/ncomms10652 [doi]
LID - 10652
AB  - 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.
FAU - Freyberg, Zachary
AU  - Freyberg Z
AD  - Department of Psychiatry, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, New York 10032, USA.
FAU - Sonders, Mark S
AU  - Sonders MS
AD  - Department of Psychiatry, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, New York 10032, USA.
AD  - Department of Neurology, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
FAU - Aguilar, Jenny I
AU  - Aguilar JI
AD  - Department of Psychiatry, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, New York 10032, USA.
FAU - Hiranita, Takato
AU  - Hiranita T
AD  - Psychobiology Section, Intramural Research Program, Department of Health and 
      Human Services, National Institute on Drug Abuse, National Institutes of Health, 
      Baltimore, Maryland 21224, USA.
FAU - Karam, Caline S
AU  - Karam CS
AD  - Department of Psychiatry, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, New York 10032, USA.
FAU - Flores, Jorge
AU  - Flores J
AD  - Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical 
      Institute, College of Physicians &Surgeons, Columbia University, New York, New 
      York 10032, USA.
FAU - Pizzo, Andrea B
AU  - Pizzo AB
AD  - Department of Psychiatry, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, New York 10032, USA.
FAU - Zhang, Yuchao
AU  - Zhang Y
AD  - Department of Psychiatry, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, New York 10032, USA.
FAU - Farino, Zachary J
AU  - Farino ZJ
AD  - Department of Psychiatry, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, New York 10032, USA.
FAU - Chen, Audrey
AU  - Chen A
AD  - Department of Psychiatry and Biobehavioral Sciences and Semel Institute for 
      Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, David Geffen 
      School of Medicine University of California, Los Angeles, California 90095, USA.
FAU - Martin, Ciara A
AU  - Martin CA
AD  - UCLA Interdepartmental Program in Molecular Toxicology, University of California, 
      Los Angeles, California 90095, USA.
FAU - Kopajtic, Theresa A
AU  - Kopajtic TA
AD  - Psychobiology Section, Intramural Research Program, Department of Health and 
      Human Services, National Institute on Drug Abuse, National Institutes of Health, 
      Baltimore, Maryland 21224, USA.
FAU - Fei, Hao
AU  - Fei H
AD  - Department of Psychiatry and Biobehavioral Sciences and Semel Institute for 
      Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, David Geffen 
      School of Medicine University of California, Los Angeles, California 90095, USA.
FAU - Hu, Gang
AU  - Hu G
AD  - Department of Chemistry, Columbia University, New York, New York 10027, USA.
FAU - Lin, Yi-Ying
AU  - Lin YY
AD  - School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 
      Republic of China 10055.
FAU - Mosharov, Eugene V
AU  - Mosharov EV
AD  - Department of Neurology, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
FAU - McCabe, Brian D
AU  - McCabe BD
AD  - Center for Motor Neuron Biology and Disease, College of Physicians &Surgeons, 
      Columbia University, New York, New York 10032, USA.
AD  - Department of Pathology and Cell Biology, College of Physicians &Surgeons, 
      Columbia University, New York, New York 10032, USA.
AD  - Department of Neuroscience, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
FAU - Freyberg, Robin
AU  - Freyberg R
AD  - Department of Psychology, Stern College for Women, Yeshiva University, New York, 
      New York 10016, USA.
FAU - Wimalasena, Kandatege
AU  - Wimalasena K
AD  - Department of Chemistry, Wichita State University, Wichita, Kansas 67260, USA.
FAU - Hsin, Ling-Wei
AU  - Hsin LW
AD  - School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 
      Republic of China 10055.
FAU - Sames, Dalibor
AU  - Sames D
AD  - Department of Chemistry, Columbia University, New York, New York 10027, USA.
FAU - Krantz, David E
AU  - Krantz DE
AD  - Department of Psychiatry and Biobehavioral Sciences and Semel Institute for 
      Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, David Geffen 
      School of Medicine University of California, Los Angeles, California 90095, USA.
FAU - Katz, Jonathan L
AU  - Katz JL
AD  - Psychobiology Section, Intramural Research Program, Department of Health and 
      Human Services, National Institute on Drug Abuse, National Institutes of Health, 
      Baltimore, Maryland 21224, USA.
FAU - Sulzer, David
AU  - Sulzer D
AD  - Department of Psychiatry, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, New York 10032, USA.
AD  - Department of Neurology, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Department of Pharmacology, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
FAU - Javitch, Jonathan A
AU  - Javitch JA
AD  - Department of Psychiatry, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
AD  - Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, New York 10032, USA.
AD  - Department of Pharmacology, College of Physicians &Surgeons, Columbia University, 
      New York, New York 10032, USA.
LA  - eng
GR  - P01 DA010154/DA/NIDA NIH HHS/United States
GR  - T32 GM007628/GM/NIGMS NIH HHS/United States
GR  - R01 MH108186/MH/NIMH NIH HHS/United States
GR  - R01 ES015747/ES/NIEHS NIH HHS/United States
GR  - GM07185/GM/NIGMS NIH HHS/United States
GR  - R01 MH086545/MH/NIMH NIH HHS/United States
GR  - R21 NS075572/NS/NINDS NIH HHS/United States
GR  - P50 AG008702/AG/NIA NIH HHS/United States
GR  - T32 ES015457/ES/NIEHS NIH HHS/United States
GR  - R01 MH107390/MH/NIMH NIH HHS/United States
GR  - P01 DA0 10154/DA/NIDA NIH HHS/United States
GR  - NS075572/NS/NINDS NIH HHS/United States
GR  - Intramural NIH HHS/United States
GR  - R01 NS075222/NS/NINDS NIH HHS/United States
GR  - K05 DA022413/DA/NIDA NIH HHS/United States
GR  - T32 GM007185/GM/NIGMS NIH HHS/United States
GR  - Howard Hughes Medical Institute/United States
GR  - R01 MH076900/MH/NIMH NIH HHS/United States
GR  - P01 DA012408/DA/NIDA NIH HHS/United States
GR  - P01 ES016732/ES/NIEHS NIH HHS/United States
GR  - AG08702/AG/NIA NIH HHS/United States
GR  - P01 DA12408/DA/NIDA NIH HHS/United States
GR  - K08 DA031241/DA/NIDA NIH HHS/United States
GR  - R01 DA007418/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160216
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Dopamine Agents)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Slc18a2 protein, rat)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 207ZZ9QZ49 (Methylphenidate)
RN  - 44RAL3456C (Methamphetamine)
RN  - CK833KGX7E (Amphetamine)
RN  - I5Y540LHVR (Cocaine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Amphetamine/*pharmacology
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Brain/*drug effects/metabolism
MH  - Cocaine/pharmacology
MH  - Dopamine/*metabolism
MH  - Dopamine Agents/*pharmacology
MH  - Dopamine Plasma Membrane Transport Proteins/*drug effects/metabolism
MH  - Dopaminergic Neurons/*drug effects/metabolism
MH  - Drosophila melanogaster
MH  - HEK293 Cells
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Locomotion/*drug effects
MH  - Methamphetamine/pharmacology
MH  - Methylphenidate/pharmacology
MH  - Optical Imaging
MH  - Rats
MH  - Synaptic Vesicles/*drug effects
MH  - Vesicular Monoamine Transport Proteins/*antagonists & inhibitors/drug 
      effects/metabolism
PMC - PMC4757768
EDAT- 2016/02/18 06:00
MHDA- 2016/06/29 06:00
PMCR- 2016/02/16
CRDT- 2016/02/17 06:00
PHST- 2015/02/02 00:00 [received]
PHST- 2016/01/06 00:00 [accepted]
PHST- 2016/02/17 06:00 [entrez]
PHST- 2016/02/18 06:00 [pubmed]
PHST- 2016/06/29 06:00 [medline]
PHST- 2016/02/16 00:00 [pmc-release]
AID - ncomms10652 [pii]
AID - 10.1038/ncomms10652 [doi]
PST - epublish
SO  - Nat Commun. 2016 Feb 16;7:10652. doi: 10.1038/ncomms10652.