PMID- 11861820
OWN - NLM
STAT- MEDLINE
DCOM- 20020328
LR  - 20190607
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 300
IP  - 3
DP  - 2002 Mar
TI  - Methylenedioxymethamphetamine decreases plasmalemmal and vesicular dopamine 
      transport: mechanisms and implications for neurotoxicity.
PG  - 1093-100
AB  - Administration of a high-dose regimen of methamphetamine (METH) rapidly and 
      profoundly decreases plasmalemmal and vesicular dopamine (DA) transport in the 
      striatum, as assessed in synaptosomes and purified vesicles, respectively. To 
      determine whether these responses were common to other amphetamines of abuse, 
      effects of methylenedioxymethamphetamine (MDMA) on the plasmalemmal DA 
      transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) were assessed. 
      Similar to effects of METH reported previously, multiple high-dose MDMA 
      administrations rapidly (within 1 h) decreased plasmalemmal DA uptake, as 
      assessed ex vivo in synaptosomes prepared from treated rats. Unlike effects of 
      multiple METH injections, this deficit was reversed completely 24 h after drug 
      treatment. Also in contrast to effects of multiple METH injections, 1) MDMA 
      caused little or no decrease in binding of the DAT ligand WIN35428, and 2) 
      neither prevention of hyperthermia nor prior depletion of DA prevented the 
      MDMA-induced reduction in plasmalemmal DA transport. However, a role for 
      phosphorylation was suggested because pretreatment with protein kinase C 
      inhibitors attenuated the deficit caused by MDMA in an in vitro model system. In 
      addition to affecting DAT function, MDMA rapidly decreased vesicular DA transport 
      as assessed in striatal vesicles prepared from treated rats. Unlike effects of 
      multiple METH injections reported previously, this decrease partially recovered 
      by 24 h after drug treatment. Taken together, these results reveal several 
      differences between effects of MDMA and previously reported METH on DAT and 
      VMAT-2; differences that may underlie the dissimilar neurotoxic profile of these 
      agents.
FAU - Hansen, J Paul
AU  - Hansen JP
AD  - Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, 
      Utah 84112, USA.
FAU - Riddle, Evan L
AU  - Riddle EL
FAU - Sandoval, Veronica
AU  - Sandoval V
FAU - Brown, Jeffrey M
AU  - Brown JM
FAU - Gibb, James W
AU  - Gibb JW
FAU - Hanson, Glen R
AU  - Hanson GR
FAU - Fleckenstein, Annette E
AU  - Fleckenstein AE
LA  - eng
GR  - DA 00869/DA/NIDA NIH HHS/United States
GR  - DA 04222/DA/NIDA NIH HHS/United States
GR  - DA11389/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Hallucinogens)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Neurotoxins)
RN  - 0 (Slc6a3 protein, rat)
RN  - 0 (Vesicular Biogenic Amine Transport Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 3466-75-9 (dihydrotetrabenazine)
RN  - 44RAL3456C (Methamphetamine)
RN  - 50370-56-4 ((1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- 
      azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester)
RN  - I5Y540LHVR (Cocaine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
RN  - Z9O08YRN8O (Tetrabenazine)
SB  - IM
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Body Temperature/drug effects
MH  - Cell Membrane/drug effects/metabolism
MH  - Cocaine/*analogs & derivatives/pharmacology
MH  - Dopamine/*metabolism
MH  - Dopamine Plasma Membrane Transport Proteins
MH  - Dopamine Uptake Inhibitors/toxicity
MH  - Hallucinogens/*toxicity
MH  - Kinetics
MH  - Male
MH  - Membrane Glycoproteins/biosynthesis
MH  - Membrane Transport Proteins/biosynthesis
MH  - Methamphetamine/toxicity
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - *Nerve Tissue Proteins
MH  - *Neuropeptides
MH  - Neurotoxins/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Synaptic Vesicles/*drug effects
MH  - Tetrabenazine/*analogs & derivatives/pharmacokinetics
MH  - Vesicular Biogenic Amine Transport Proteins
MH  - Vesicular Monoamine Transport Proteins
EDAT- 2002/02/28 10:00
MHDA- 2002/03/29 10:01
CRDT- 2002/02/28 10:00
PHST- 2002/02/28 10:00 [pubmed]
PHST- 2002/03/29 10:01 [medline]
PHST- 2002/02/28 10:00 [entrez]
AID - 10.1124/jpet.300.3.1093 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2002 Mar;300(3):1093-100. doi: 10.1124/jpet.300.3.1093.