The monoamine oxidase-B inhibitor L-deprenyl protects against 3,4-methylenedioxymethamphetamine-induced lipid peroxidation and long-term serotonergic deficits.
Journal of Pharmacology and Experimental Therapeutics May 1, 1995 DOI: 10.1016/s0022-3565(25)09490-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | MDMA L-deprenyl |
| Dose | MDMA 40 mg/kg; L-deprenyl 2 mg/kg |
| Duration | Assessments at 12 hours, 18 hours, and 7 days after treatment |
| Measures | [3H]paroxetine binding, 5-HT levels, 5-HIAA levels, thiobarbituric acid reactive substances, malondialdehyde formation, tryptophan hydroxylase activity, [3H]dopamine uptake |
| Topics | Serotonin MDMA |
| Keywords | Brain Synaptosomes Animals Rats, sprague-dawley N-methyl-3,4-methylenedioxyamphetamine Selegiline Hydroxyindoleacetic acid Tryptophan hydroxylase Monoamine oxidase inhibitors Lipid peroxidation Male |
| Key findings | MDMA at 40 mg/kg decreased serotonin uptake sites and serotonin and 5-HIAA levels in three brain regions at seven days and increased lipid peroxidation at 12 hours and reduced tryptophan hydroxylase activity at 18 hours; the MAO-B inhibitor L-deprenyl blocked these effects. The authors propose that MAO-B deamination of excess dopamine in serotonin terminals generates hydrogen peroxide, leading to oxidative damage and selective serotonin terminal degeneration. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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