PMID- 19076925
OWN - NLM
STAT- MEDLINE
DCOM- 20090805
LR  - 20131121
IS  - 1369-1600 (Electronic)
IS  - 1355-6215 (Linking)
VI  - 14
IP  - 2
DP  - 2009 Apr
TI  - Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: 
      influence of monoamine oxidase type A.
PG  - 185-93
LID - 10.1111/j.1369-1600.2008.00143.x [doi]
AB  - The administration of a neurotoxic dose of 3,4-methylenedioxymethamphetamine 
      (MDMA; 'ecstasy') to the rat results in mitochondrial oxidative damage in the 
      central nervous system, namely lipid and protein oxidation and mitochondrial DNA 
      deletions with subsequent impairment of the correspondent protein expression. 
      Although these toxic effects were shown to be prevented by monoamine oxidase B 
      inhibition, the role of monoamine oxidase A (MAO-A) in MDMA-mediated 
      mitochondrial damage remains to be evaluated. Thus, the aim of the present study 
      was to clarify the potential interference of a specific inhibition of MAO-A by 
      clorgyline, on the deleterious effects produced by a binge administration of a 
      neurotoxic dose of MDMA (10 mg MDMA/kg of body weight, intraperitoneally, every 2 
      hours in a total of four administrations) to an adolescent rat model. The 
      parameters evaluated were mitochondrial lipid peroxidation, protein carbonylation 
      and expression of the respiratory chain protein subunits II of reduced 
      nicotinamide adenine dinucleotide dehydrogenase (NDII) and I of cytochrome 
      oxidase (COXI). Considering that hyperthermia has been shown to contribute to the 
      neurotoxic effects of MDMA, another objective of the present study was to 
      evaluate the body temperature changes mediated by MDMA with a MAO-A selective 
      inhibition by clorgyline. The obtained results demonstrated that the 
      administration of a neurotoxic binge dose of MDMA to an adolescent rat model 
      previously treated with the specific MAO-A inhibitor, clorgyline, resulted in 
      synergistic effects on serotonin- (5-HT) mediated behaviour and body temperature, 
      provoking high mortality. Inhibition of MAO-A by clorgyline administration had no 
      protective effect on MDMA-induced alterations on brain mitochondria (increased 
      lipid peroxidation, protein carbonylation and decrease in the expression of the 
      respiratory chain subunits NDII and COXI), although it aggravated MDMA-induced 
      decrease in the expression of COXI. These results reinforce the notion that the 
      concomitant use of MAO-A inhibitors and MDMA is counter indicated because of the 
      resulting severe synergic toxicity.
FAU - Alves, Ema
AU  - Alves E
AD  - Grupo Neurocomportamento, Instituto de Biologia Molecular e Celular (IBMC), 
      University of Porto (UP), Porto, Portugal.
FAU - Summavielle, Teresa
AU  - Summavielle T
FAU - Alves, Cecilia Juliana
AU  - Alves CJ
FAU - Custodio, Jose Barata Antunes
AU  - Custodio JB
FAU - Fernandes, Eduarda
AU  - Fernandes E
FAU - de Lourdes Bastos, Maria
AU  - de Lourdes Bastos M
FAU - Tavares, Maria Amelia
AU  - Tavares MA
FAU - Carvalho, Felix
AU  - Carvalho F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081212
PL  - United States
TA  - Addict Biol
JT  - Addiction biology
JID - 9604935
RN  - 0 (Hallucinogens)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain/*drug effects/*enzymology/metabolism
MH  - Hallucinogens/*adverse effects
MH  - Lipid Peroxidation/drug effects
MH  - Mitochondria/*drug effects/*enzymology
MH  - Monoamine Oxidase/*metabolism
MH  - Monoamine Oxidase Inhibitors/*pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurotoxicity Syndromes/enzymology
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Wistar
EDAT- 2008/12/17 09:00
MHDA- 2009/08/06 09:00
CRDT- 2008/12/17 09:00
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/08/06 09:00 [medline]
AID - ADB143 [pii]
AID - 10.1111/j.1369-1600.2008.00143.x [doi]
PST - ppublish
SO  - Addict Biol. 2009 Apr;14(2):185-93. doi: 10.1111/j.1369-1600.2008.00143.x. Epub 
      2008 Dec 12.