PMID- 15056723
OWN - NLM
STAT- MEDLINE
DCOM- 20040618
LR  - 20231013
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 24
IP  - 13
DP  - 2004 Mar 31
TI  - Methamphetamine increases dopamine transporter higher molecular weight complex 
      formation via a dopamine- and hyperthermia-associated mechanism.
PG  - 3436-43
AB  - Multiple high-dose administrations of methamphetamine (METH) both rapidly (within 
      hours) decrease plasmalemmal dopamine (DA) uptake and cause long-term deficits in 
      DA transporter (DAT) levels and other dopaminergic parameters persisting weeks to 
      months in rat striatum. In contrast, either a single administration of METH or 
      multiple administrations of methylenedioxymethamphetamine (MDMA) cause less of an 
      acute reduction in DA uptake and little or no persistent dopaminergic deficits. 
      The long-term dopaminergic deficits caused by METH have been suggested, in part, 
      to involve the DAT. Hence, this study assessed the impact of METH and MDMA 
      administration on the DAT protein per se. Results revealed that multiple 
      administrations of METH promoted formation of higher molecular weight (>170 kDa) 
      DAT-associated protein complexes 24-48 hr after treatment. This increase was 
      attenuated by either preventing hyperthermia or pretreatment with the tyrosine 
      hydroxylase inhibitor alpha-methyl-p-tyrosine; notably, each of these 
      manipulations has also been demonstrated previously to prevent the persistent 
      deficits in dopaminergic function caused by METH treatment. In contrast, either a 
      single injection of METH or multiple injections of MDMA caused little or no 
      formation of these DAT complexes. The addition of the reducing agent 
      beta-mercaptoethanol to samples prepared from METH-treated rats diminished the 
      intensity of these complexes. Taken together, these data are the first to 
      demonstrate higher molecular weight DAT complex formation in vivo and that such 
      formation can be altered by both pharmacological and physiological manipulations. 
      The implications of this phenomenon with regard to the neurotoxic potential of 
      these stimulants are discussed.
FAU - Baucum, Anthony J 2nd
AU  - Baucum AJ 2nd
AD  - Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, 
      Utah 84112, USA.
FAU - Rau, Kristi S
AU  - Rau KS
FAU - Riddle, Evan L
AU  - Riddle EL
FAU - Hanson, Glen R
AU  - Hanson GR
FAU - Fleckenstein, Annette E
AU  - Fleckenstein AE
LA  - eng
GR  - R01 DA000869/DA/NIDA NIH HHS/United States
GR  - DA13367/DA/NIDA NIH HHS/United States
GR  - DA11389/DA/NIDA NIH HHS/United States
GR  - R01 DA004222/DA/NIDA NIH HHS/United States
GR  - K05 DA000378/DA/NIDA NIH HHS/United States
GR  - R01 DA011389/DA/NIDA NIH HHS/United States
GR  - DA00869/DA/NIDA NIH HHS/United States
GR  - DA00378/DA/NIDA NIH HHS/United States
GR  - R29 DA011389/DA/NIDA NIH HHS/United States
GR  - P01 DA013367/DA/NIDA NIH HHS/United States
GR  - DA04222/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Slc6a3 protein, rat)
RN  - 44RAL3456C (Methamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Amphetamine-Related Disorders/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - Dopamine/*metabolism
MH  - Dopamine Plasma Membrane Transport Proteins
MH  - Dopamine Uptake Inhibitors/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Fever/chemically induced/*physiopathology/prevention & control
MH  - Macromolecular Substances
MH  - Male
MH  - *Membrane Glycoproteins
MH  - Membrane Transport Proteins/*drug effects/*metabolism
MH  - Methamphetamine/*pharmacology
MH  - Molecular Weight
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Nerve Tissue Proteins/*drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Time
PMC - PMC6730025
EDAT- 2004/04/02 05:00
MHDA- 2004/06/24 05:00
PMCR- 2004/09/30
CRDT- 2004/04/02 05:00
PHST- 2004/04/02 05:00 [pubmed]
PHST- 2004/06/24 05:00 [medline]
PHST- 2004/04/02 05:00 [entrez]
PHST- 2004/09/30 00:00 [pmc-release]
AID - 24/13/3436 [pii]
AID - 10.1523/JNEUROSCI.0387-04.2004 [doi]
PST - ppublish
SO  - J Neurosci. 2004 Mar 31;24(13):3436-43. doi: 10.1523/JNEUROSCI.0387-04.2004.