Whoops. My left-click is screwed up, sorry about that.
Medievil, thanks for those, it seems there may be more to this than I thought and you are definitely making me re-evaluate. With regards to the third abstract, it appears that an NMDA antagonist diminished the toxicity of benzodiazepine withdrawal during the period that toxic symptoms appear in the rat, which is not surprising and certainly something an NMDA antagonist should do. Note this does not speak to benzodiazepine tolerance in terms of diminished effect however.
The second abstract and first contain some more interesting data, the second being the strongest, although I have to remain skeptical at this point, due to contradictory data in other research (which you mention) and some confusing things or perhaps caveats found in the abstracts as well. It is important to get clarification on certain terms and what partial tolerance constitutes in this study ... as well as 'learned and unlearned tolerance', which is an unusual description. I hope to get a hold of the full texts of these.
Personally i'm inclined to beleive that memantine does in fact prevent tolerance to the anxiolytic effects too (beleiving the anecdotal reports)
If we're making predictions, I think ultimately I may have to settle for a more complex view of this issue, because even if dopaminergic mechanisms is the only thing about benzodiazepine effects that memantine touches, then that would still change benzodiazepine tolerance, because none of these systems stand alone. Mesolimbic dopamine is certainly intimately related to one other major system with depressant tendencies, the endogenous opioid system.
(Hence my interest in descriptors like partial tolerance)
But I think it's important, healthy to retain doubt in these cases ... not until there's more information. This goes for memantine and amphetamine as well as memantine and benzodiazepines.
the reason why that wasnt the case in that seperate rat study is imo because they used a differend NMDA antagonist then memantine, ive seen that they can behave differendly (for example recently saw a study showing NMDA antagonist 1 prevented both tolerance by repeated dosing, and tolerance induced by social defeat, however memantine only prevented tolerance to repeated dosing and not that induced by social defeat) so differend NMDA antagonists can behave differendly wheter thats the reason i dont know, but thats my gues about whats going on.
It's certainly the case that NMDA antagonists can differ vastly and memantine especially has a number of unusual properties, although this doesn't say anything specific.
Edited by graatch, 24 June 2010 - 07:59 AM.