PMID- 16098955
OWN - NLM
STAT- MEDLINE
DCOM- 20051207
LR  - 20131121
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1056
IP  - 2
DP  - 2005 Sep 21
TI  - Evidence for a role of energy dysregulation in the MDMA-induced depletion of 
      brain 5-HT.
PG  - 168-75
AB  - Although the exact mechanism involved in the long-term depletion of brain 
      serotonin (5-HT) produced by substituted amphetamines is not completely known, 
      evidence suggests that oxidative and/or bioenergetic stress may contribute to 
      3,4-methylenedioxymethamphetamine (MDMA)-induced 5-HT toxicity. In the present 
      study, the effect of supplementing energy substrates was examined on the 
      long-term depletion of striatal 5-HT and dopamine produced by the local perfusion 
      of MDMA (100 microM) and malonate (100 mM) and the depletion of striatal and 
      hippocampal 5-HT concentrations produced by the systemic administration of MDMA 
      (10 mg/kg i.p. x4). The effect of systemic administration of MDMA on ATP levels 
      in the striatum and hippocampus also was examined. Reverse dialysis of MDMA and 
      malonate directly into the striatum resulted in a 55-70% reduction in striatal 
      concentrations of 5-HT and dopamine, and these reductions were significantly 
      attenuated when MDMA and malonate were co-perfused with nicotinamide (1 mM). 
      Perfusion of nicotinamide or ubiquinone (100 microM) also attenuated the 
      depletion of 5-HT in the striatum and hippocampus produced by the systemic 
      administration of MDMA. Finally, the systemic administration of MDMA produced a 
      30% decrease in the concentration of ATP in the striatum and hippocampus. These 
      results support the conclusion that MDMA produces a dysregulation of energy 
      metabolism which contributes to the mechanism of MDMA-induced 5-HT neurotoxicity.
FAU - Darvesh, Altaf S
AU  - Darvesh AS
AD  - College of Pharmacy, University of Cincinnati, 3223, Eden Ave., Cincinnati, OH 
      45267, USA.
FAU - Gudelsky, Gary A
AU  - Gudelsky GA
LA  - eng
GR  - DA07427/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Malonates)
RN  - 0 (Serotonin Agents)
RN  - 1339-63-5 (Ubiquinone)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 333DO1RDJY (Serotonin)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9KX7ZMG0MK (malonic acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Brain/anatomy & histology/*drug effects/metabolism
MH  - Brain Chemistry/drug effects
MH  - Dopamine/metabolism
MH  - Drug Interactions
MH  - Energy Metabolism/*drug effects
MH  - Male
MH  - Malonates/pharmacology
MH  - Microdialysis/methods
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Niacinamide/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/*toxicity
MH  - Time Factors
MH  - Ubiquinone/pharmacology
EDAT- 2005/08/16 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/08/16 09:00
PHST- 2005/01/20 00:00 [received]
PHST- 2005/07/07 00:00 [revised]
PHST- 2005/07/13 00:00 [accepted]
PHST- 2005/08/16 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/08/16 09:00 [entrez]
AID - S0006-8993(05)01048-6 [pii]
AID - 10.1016/j.brainres.2005.07.009 [doi]
PST - ppublish
SO  - Brain Res. 2005 Sep 21;1056(2):168-75. doi: 10.1016/j.brainres.2005.07.009.