Role of excitotoxicity in MDMA/Meth damage/tolerance

[VelocideX]

I've always been curious about whether excitotoxicity plays a role in Meth/MDMA tolerance and/or axon damage.

A search of pubmed has a few links which suggest that excitotoxicity MAY play a role in methamphetamine damage due to mitochondrial dysfunction, but there's not really all that much there.

Do any of you think that excitotoxicity may play a role?

What about in tolerance? There's been a few research reports in recent times that NMDA antagonists may prevent or slow opiate tolerance. this thread postulates that a similar mechanism occurs in regards to meth tolerance. The implication is that excitotoxicity is to blame for what some people experience as long-term tolerance (~months or years), and gives suggestions for preventing it.

Again, any thoughts?

Though the thread above gives NMDA antagonists as a suggestion for preventing this, are there any others? Acetyl-l-carnitine (mentioned in two studies on pubmed -- search for excitotoxicity and amphetamine) and CoQ10 seem to both ameliorate excitotoxicity, but I'm wondering if there's anything else. Am I just being fanciful about it's potential for damage?

 

[BilZ0r]

It's just not going to be excitotoxicity. For one, excitotoxicity isn't terminal specific, it kills neurons dead. Excitotoxicity is also not specific for dopaminergic cell types, it would spill onto non-dopaminergic neurons. And, as far as I'm awear, so long as you avoid the hypothermia inducing effects of NMDA antagonists, the don't protect against meth-induced neurtoxocity

The ability for NMDA antagonists to block tolerance is a rather general phenomenia, and probably stems from the reduced intracellular Ca2+, and hence Ca2+ dependent kinase activity you would see. Protein kinase C downregulates a bunch of receptors....

I can find studies mentioning l-carnitine, not an acetylated version...