PMID- 11170222
OWN - NLM
STAT- MEDLINE
DCOM- 20010503
LR  - 20181130
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 40
IP  - 1
DP  - 2001 Apr
TI  - Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl 
      radical formation and the behavioral and neurochemical consequences of the 
      depletion of brain 5-HT.
PG  - 55-64
AB  - MDMA-induced 5-HT neurotoxicity has been proposed to involve oxidative stress due 
      to increased formation of hydroxyl radicals. Recently, MDMA-induced 5-HT 
      neurotoxicity has been shown to be accompanied by a suppression of behavioral and 
      neurochemical responses to a subsequent injection of MDMA. The intent of the 
      present study was to examine whether suppression of the MDMA-induced formation of 
      hydroxyl radicals by an antioxidant, ascorbic acid, attenuates both the 
      MDMA-induced depletion of 5-HT and the functional consequences associated with 
      this depletion. Treatment of rats with ascorbic acid suppressed the generation of 
      hydroxyl radicals, as evidenced by the production of 2,3-dihydroxybenzoic acid 
      from salicylic acid, in the striatum during the administration of a neurotoxic 
      regimen of MDMA. Ascorbic acid also attenuated the MDMA-induced depletion of 
      striatal 5-HT content. In rats treated with a neurotoxic regimen of MDMA, the 
      ability of a subsequent injection of MDMA to increase the extracellular 
      concentration of 5-HT in the striatum, elicit the 5-HT behavioral syndrome, and 
      produce hyperthermia was markedly reduced compared to the responses in control 
      rats. The concomitant administration of ascorbic acid with the neurotoxic regimen 
      of MDMA prevented the diminished neurochemical and behavioral responses to a 
      subsequent injection of MDMA. Finally, a neurotoxic regimen of MDMA produced 
      significant reductions in the concentrations of vitamin E and ascorbic acid in 
      the striatum and hippocampus. Thus, the MDMA-induced depletion of brain 5-HT and 
      the functional consequences thereof appear to involve the induction of oxidative 
      stress resulting from an increased generation of free radicals and diminished 
      antioxidant capacity of the brain.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Shankaran, M
AU  - Shankaran M
AD  - College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267-0004, USA.
FAU - Yamamoto, B K
AU  - Yamamoto BK
FAU - Gudelsky, G A
AU  - Gudelsky GA
LA  - eng
GR  - DA 07427/DA/NIDA NIH HHS/United States
PT  - Journal Article
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 (Antioxidants)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Serotonin Agents)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - PQ6CK8PD0R (Ascorbic Acid)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Ascorbic Acid/metabolism/*pharmacology
MH  - Behavior, Animal/drug effects/physiology
MH  - Brain/*drug effects/metabolism/physiopathology
MH  - Dopamine/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Fever/chemically induced/metabolism/physiopathology
MH  - Hippocampus/drug effects/metabolism/physiopathology
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neostriatum/drug effects/metabolism/physiopathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*deficiency
MH  - Serotonin Agents/*pharmacology
EDAT- 2001/02/15 11:00
MHDA- 2001/05/05 10:01
CRDT- 2001/02/15 11:00
PHST- 2001/02/15 11:00 [pubmed]
PHST- 2001/05/05 10:01 [medline]
PHST- 2001/02/15 11:00 [entrez]
AID - 10.1002/1098-2396(200104)40:1<55::AID-SYN1026>3.0.CO;2-O [pii]
AID - 10.1002/1098-2396(200104)40:1<55::AID-SYN1026>3.0.CO;2-O [doi]
PST - ppublish
SO  - Synapse. 2001 Apr;40(1):55-64. doi: 
      10.1002/1098-2396(200104)40:1<55::AID-SYN1026>3.0.CO;2-O.