The monoamine oxidase-B inhibitor L-deprenyl protects against 3,4-methylenedioxymethamphetamine-induced lipid peroxidation and long-term serotonergic deficits
by
Sprague JE, Nichols DE
Department of Pharmacology and Toxicology,
School of Pharmacy and Pharmacal Sciences,
Purdue University, West Lafayette, Indiana, USA.
J Pharmacol Exp Ther 1995 May; 273(2): 667-73
ABSTRACT3,4-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.MAO
MDMA
Raves
MAO-b
Serotonin
Dopamine
L-deprenyl
Entactogens
Empathogens
Candyflipping
Ecstasy and sex
Protect and survive
Ecstasy and immunity
Ecstasy and fluoxetine
Ecstasy and tryptophan
Tryptophan hydroxylase
MDMA: pharmacokinetics
Ecstasy, dopamine and serotonin
MDMA neurotoxicity : the role of MAO-b
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