PMID- 8584978
OWN - NLM
STAT- MEDLINE
DCOM- 19960319
LR  - 20131121
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 21
IP  - 2
DP  - 1995 Oct
TI  - Superoxide radicals mediate the biochemical effects of 
      methylenedioxymethamphetamine (MDMA): evidence from using CuZn-superoxide 
      dismutase transgenic mice.
PG  - 169-76
AB  - The subacute and long-term biochemical effects of methylenedioxymethamphetamine 
      (MDMA) were assessed in homozygous and heterozygous transgenic (Tg) mice that 
      carry the complete sequence of the human copper-zinc (CuZn) superoxide dismutase 
      (SOD) gene. Non-transgenic (Non-Tg) mice showed significant decreased in striatal 
      dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels both at 24 h and at 2 
      weeks after a single injection of MDMA (50 mg/kg). Heterozygous SOD-Tg mice 
      showed DA depletion only at the 24 h time point. In contrast, homozygous SOD-Tg 
      mice show no DA or DOPAC depletion at either the 24 h or at the 2 week time 
      points. Moreover, three injections of MDMA (50 mg/kg) given 24 h apart also 
      caused marked reduction of striatal DA and DOPAC in Non-Tg mice when these 
      substances were measured 2 weeks after the last MDMA injection. That injection 
      schedule also caused small decreases in DA levels in the heterozygous animals but 
      no changes in the homozygous mice; DOPAC levels were not affected in the 
      heterozygous nor in the homozygous SOD-Tg mice. Furthermore, the multiple 
      injection schedule caused significant decreases in DA and DOPAC in female Non-Tg 
      mice but not in the two strains of transgenic mice. Neither the single dose nor 
      the multiple dose schedule of MDMA injections affected striatal serotonin (5-HT) 
      and 5-hydroxyindoleacetic acid (5-HIAA) levels in any of the three strains of 
      mice. These results support previous observations that MDMA-induced biochemical 
      effects are observed in the DA systems of mice, whereas these effects are seen in 
      the 5-HT systems of rats. The present observations also document for the first 
      time a role for the production of superoxide radicals in these effects of MDMA. 
      These mice are an important tool for dissecting pathways involved in drug-induced 
      neurotoxicity.
FAU - Cadet, J L
AU  - Cadet JL
AD  - Molecular Neuropsychiatry Section, NIH/NIDA, Baltimore, Maryland 21224, USA.
FAU - Ladenheim, B
AU  - Ladenheim B
FAU - Hirata, H
AU  - Hirata H
FAU - Rothman, R B
AU  - Rothman RB
FAU - Ali, S
AU  - Ali S
FAU - Carlson, E
AU  - Carlson E
FAU - Epstein, C
AU  - Epstein C
FAU - Moran, T H
AU  - Moran TH
LA  - eng
GR  - AG-08938/AG/NIA NIH HHS/United States
GR  - HD 24605/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Receptors, Dopamine)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 11062-77-4 (Superoxides)
RN  - 146145-21-3 (RTI 121)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - I5Y540LHVR (Cocaine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH  - Animals
MH  - Autoradiography
MH  - Cocaine/analogs & derivatives/pharmacokinetics
MH  - Corpus Striatum/metabolism
MH  - Dopamine/metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic/genetics
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Receptors, Dopamine/metabolism
MH  - Superoxide Dismutase/genetics
MH  - Superoxides/*metabolism
MH  - Tissue Distribution
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
AID - 10.1002/syn.890210210 [doi]
PST - ppublish
SO  - Synapse. 1995 Oct;21(2):169-76. doi: 10.1002/syn.890210210.