PMID- 9374204
OWN - NLM
STAT- MEDLINE
DCOM- 19971223
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 769
IP  - 2
DP  - 1997 Sep 26
TI  - Differential toxic effects of methamphetamine (METH) and 
      methylenedioxymethamphetamine (MDMA) in multidrug-resistant (mdr1a) knockout 
      mice.
PG  - 340-6
AB  - The toxic effects of methamphetamine (METH) (2.5, 5.0 and 10.0 mg/kg) and 
      methylenedioxymethamphetamine (MDMA) (5.0, 10.0 and 20.0 mg/kg) on dopaminergic 
      systems were assessed in the striatum and of the nucleus accumbens in mdr1a 
      wild-type and knockout mice. METH caused significant dose-dependent decreases of 
      dopamine (DA) and DA transporters (DAT) in the striatum and the nucleus accumbens 
      (NAc) of both wild-type and knockout mice. The lowest doses of METH (2.5 mg/kg) 
      caused only small changes in the wild-type, but marked. decreases in the mdr1a 
      knockout mice. The two higher doses (5 mg/kg and 10 mg/kg) caused similar changes 
      in both strains of mice. In contrast to METH, MDMA caused greater percentage 
      decreases in DAT in the wild-type mice. For example, the lowest dose (5 mg/kg) 
      caused significant decreases in DAT in the NAc of wild-type but not of mdr1a 
      knockout mice. The highest dose (20 mg/kg) caused similar changes in both the 
      strains. These results suggest that METH and MDMA interact differentially with 
      P-glycoproteins. These observations document, for the first time, a role for 
      these proteins in the entry of METH and MDMA into the brain via the blood-brain 
      barrier, with P-glycoprotein possibly facilitating the entry of MDMA but 
      interfering with that of METH into the brain.
FAU - Mann, H
AU  - Mann H
AD  - Molecular Neuropsychiatry Section, NIDA, Addiction Research Center, Baltimore, MD 
      21224, USA.
FAU - Ladenheim, B
AU  - Ladenheim B
FAU - Hirata, H
AU  - Hirata H
FAU - Moran, T H
AU  - Moran TH
FAU - Cadet, J L
AU  - Cadet JL
LA  - eng
GR  - HD 24605/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Serotonin Agents)
RN  - 44RAL3456C (Methamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Binding Sites/drug effects
MH  - Corpus Striatum/drug effects/metabolism
MH  - Dopamine/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Genes, MDR/*genetics
MH  - Male
MH  - Methamphetamine/*poisoning
MH  - Mice
MH  - Mice, Knockout/*genetics
MH  - Mice, Mutant Strains
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*poisoning
MH  - Nucleus Accumbens/drug effects/metabolism
MH  - Serotonin Agents/*poisoning
EDAT- 1997/11/28 00:00
MHDA- 1997/11/28 00:01
CRDT- 1997/11/28 00:00
PHST- 1997/11/28 00:00 [pubmed]
PHST- 1997/11/28 00:01 [medline]
PHST- 1997/11/28 00:00 [entrez]
AID - S0006-8993(97)00754-3 [pii]
AID - 10.1016/s0006-8993(97)00754-3 [doi]
PST - ppublish
SO  - Brain Res. 1997 Sep 26;769(2):340-6. doi: 10.1016/s0006-8993(97)00754-3.