PMID- 7538579
OWN - NLM
STAT- MEDLINE
DCOM- 19950619
LR  - 20151119
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 273
IP  - 2
DP  - 1995 May
TI  - The monoamine oxidase-B inhibitor L-deprenyl protects against 
      3,4-methylenedioxymethamphetamine-induced lipid peroxidation and long-term 
      serotonergic deficits.
PG  - 667-73
AB  - 3,4-Methylenedioxymethamphetamine (MDMA)-induced serotonergic neurotoxicity was 
      assessed in the striatum, hippocampus and frontal cortex of rats by using 
      [3H]paroxetine binding to label serotonin (5-HT) uptake sites and 5-HT and 
      5-hydroxyindoleacetic acid (5-HIAA) levels as markers of serotonergic function. 
      NMDA (40 mg/kg) induced a significant decrease in both [3H]paroxetine binding 
      Bmax and 5-HT and 5-HIAA levels 7 days after treatment. The monoamine oxidase-B 
      inhibitor L-deprenyl (2 mg/kg) administered 30 min before MDMA blocked these 
      decreases. MDMA (40 mg/kg) also maximally increased the formation of 
      thiobarbituric acid reactive substances (an indicator of lipid peroxidation) 12 
      hr after treatment in all three brain regions studied. This increase in 
      malondialdehyde formation was also blocked by pretreatment with L-deprenyl. 
      Tryptophan hydroxylase (TPH) activity was also significantly reduced 18 hr after 
      MDMA. L-Deprenyl reversed this decrease in TPH activity. Another experiment 
      confirmed that a significant fraction of [3H]dopamine uptake into hippocampal 
      synaptosomes was blocked by 500 nM fluoxetine, a selective 5-HT uptake inhibitor. 
      These data suggest that the deamination by monoamine oxidase-B of excessive 
      dopamine within the 5-HT terminal generates hydrogen peroxide that may lead to 
      membrane lipid peroxidation, and perhaps other oxidative insults, resulting in 
      selective 5-HT terminal degeneration subsequent to MDMA treatment.
FAU - Sprague, J E
AU  - Sprague JE
AD  - Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal 
      Sciences, Purdue University, West Lafayette, Indiana, USA.
FAU - Nichols, D E
AU  - Nichols DE
LA  - eng
GR  - DA-04758/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 2K1V7GP655 (Selegiline)
RN  - 333DO1RDJY (Serotonin)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/enzymology/metabolism
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Lipid Peroxidation/*drug effects
MH  - Male
MH  - Monoamine Oxidase Inhibitors/*pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Selegiline/*pharmacology
MH  - Serotonin/*deficiency/metabolism
MH  - Synaptosomes/drug effects/metabolism
MH  - Tryptophan Hydroxylase/metabolism
EDAT- 1995/05/01 00:00
MHDA- 1995/05/01 00:01
CRDT- 1995/05/01 00:00
PHST- 1995/05/01 00:00 [pubmed]
PHST- 1995/05/01 00:01 [medline]
PHST- 1995/05/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1995 May;273(2):667-73.