Re: MAPS: The role of heat and dopamine in MDMA neurotoxicity

["Nicholas V. Cozzi, Ph.D." <nvcozzi@xxxxxxxxxxxxxxxx>]

At 06:23 AM 8/31/2002 +0000, Little John wrote:

>        Interestingly, the research also depleted serotonin supplies, but
> again, when temps were increased this did not protect the rats.

What hasn't been mentioned is the fact that excessive 5-HT release will
itself produce hyperthermia.  One of 5-HT's major roles is in
thermoregulation.  Hadn't heard about dopamine's involvement in temperature
control though.

Regarding whether the temperature rise is enough to be neurotoxic, once you
hit about 40 oC (104 oF) or so, you induce so-called heat shock proteins
which are supposed to help cells survive.  It is possible that some
as-yet-unknown interaction between HSPs and an MDMA metabolite occurs which
results in changes in axon morphology and 5-HT levels.  An earlier
discussion on this list (with citations provided) pointed out that direct
injection of MDMA into the brain does not produce the neuronal
changes.  This argues strongly for a metabolite being the culprit.

Nicholas V. Cozzi, Ph.D.
Department of Pharmacology and Toxicology
Brody School of Medicine
East Carolina University
Greenville, NC  27834



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