PMID- 11299327
OWN - NLM
STAT- MEDLINE
DCOM- 20010517
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 77
IP  - 2
DP  - 2001 Apr
TI  - Enhancement of 3,4-methylenedioxymethamphetamine neurotoxicity by the energy 
      inhibitor malonate.
PG  - 647-54
AB  - The acute and long-term effects of the local perfusion of 
      3,4-methylenedioxymethamphetamine (MDMA) and the interaction with the 
      mitochondrial inhibitor malonate (MAL) were examined in the rat striatum. MDMA, 
      MAL or the combination of MAL with MDMA was reverse dialyzed into the striatum 
      for 8 h via a microdialysis probe while extracellular dopamine (DA) and serotonin 
      (5-HT) were measured. One week later, tissue immediately surrounding the probe 
      was assayed for DA and 5-HT tissue content. Local perfusion of MDMA increased DA 
      and 5-HT release but did not produce long-term depletion of DA or 5-HT in tissue. 
      Malonate also increased both DA and 5-HT release but, in contrast to MDMA, 
      produced only long-term depletion of DA. The combined perfusion of MDMA/MAL 
      synergistically increased the release of DA and 5-HT and produced long-term 
      depletion of both DA and 5-HT in tissue. These results support the conclusion 
      that DA, compared with 5-HT, neurons are more susceptible to mitochondrial 
      inhibition. Moreover, MDMA, which does not normally produce DA depletion in the 
      rat, exacerbated MAL-induced DA depletions. The effect of MDMA in combination 
      with MAL to produce 5-HT depletion suggests a role for bio-energetic stress in 
      MDMA-induced toxicity to 5-HT neurons. Overall, these results highlight the 
      importance of energy balance to the function of DA and 5-HT neurons and to the 
      toxic effects of MDMA.
FAU - Nixdorf, W L
AU  - Nixdorf WL
AD  - Program in Basic and Clinical Neuroscience, Department of Psychiatry, Case 
      Western Reserve University, Cleveland, USA.
FAU - Burrows, K B
AU  - Burrows KB
FAU - Gudelsky, G A
AU  - Gudelsky GA
FAU - Yamamoto, B K
AU  - Yamamoto BK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Malonates)
RN  - 0 (Serotonin Agents)
RN  - 333DO1RDJY (Serotonin)
RN  - 9KX7ZMG0MK (malonic acid)
RN  - EC 1.3.99.1 (Succinate Dehydrogenase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Corpus Striatum/chemistry
MH  - Dopamine/metabolism
MH  - Drug Synergism
MH  - Energy Metabolism/*drug effects
MH  - Enzyme Inhibitors/pharmacology/toxicity
MH  - Extracellular Space/chemistry
MH  - Male
MH  - Malonates/pharmacology/*toxicity
MH  - Microdialysis
MH  - Mitochondria/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/metabolism
MH  - Serotonin Agents/pharmacology/*toxicity
MH  - Succinate Dehydrogenase/antagonists & inhibitors
EDAT- 2001/04/12 10:00
MHDA- 2001/05/18 10:01
CRDT- 2001/04/12 10:00
PHST- 2001/04/12 10:00 [pubmed]
PHST- 2001/05/18 10:01 [medline]
PHST- 2001/04/12 10:00 [entrez]
AID - 10.1046/j.1471-4159.2001.00262.x [doi]
PST - ppublish
SO  - J Neurochem. 2001 Apr;77(2):647-54. doi: 10.1046/j.1471-4159.2001.00262.x.