MAPS: Strange info on MDMA tox

["'David' M. Perlman" <dump@xxxxxxxxxxxxxxxx>]

Here is something I found while searching for something unrelated on
Medline (see
http://www.biomednet.com/db/medline?Command=Record&RecID01=95271481 ).

"NMDA" (below) seems to be a typo. The picture they are presenting here
seems to be that the supposed 5-HT toxicity of MDMA occurs when the MDMA
somehow causes there to be too much _dopamine_ in a _serotonergic_
synapse, which is then transported by the _serotonin_ reuptake transporter
in to, I assume, the presynaptic side, where it is oxidized by MAO-B,
releasing destructive hydrogen peroxide. 

Does this make sense to anyone?  I don't understand why MDMA would put
dopamine where serotonin should be; or why the serotonin transporter would
transport dopamine.  Any explanation would be greatly appreciated... 

Here's the 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.
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-dave----------------------------------------------------------------
There's a fine line between enlightened anarchy and total laziness.
-John Leighton Beezer


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