Posted by Ame Sans Vie on January 12, 2004, at 10:08:23
In reply to Re: A question/concern about 5-HT reuptake inhibition » Ame Sans Vie, posted by mattdds on January 9, 2004, at 16:16:58
Hiya Matt,
> ASV,
>
> Or should I say Mike? Michael?Mike's fine. :-)
> You bring up some interesting issues that I have thought about as well.
>
> First, though, what exactly do you mean by "undue stress"? Define "stress" in this context. And what potential problems might arise from it? I'm not asking sarcastically, but it would help if you clarified what you meant by that.Well, I don't mean emotional stress. I'm talking about stress on our nervous systems from overworking. There's a better explanation in my post to PoohBear.
> First off, let me start by saying that I think we really have *no* idea how antidepressants are working, but that they seem to certainly work in some people.
>
> As I'm sure you're well aware, the brain is amazingly plastic. When there is too much serotonin, for example, in the synapses, compensatory mechanisms like receptor down regulation or desensitization will kick in to ensure that the serotonergic (or DA-ergic, or NE-ergic, etc.) "tone" is not too high.
>
> So you have all this excess serotonin floating around in the synapse, and initially, this creates strain on the system, but after downregulation of postsynaptic receptors, the net serotonergic transmission should be similar to what it was originally.
>
> This is what has always perplexed me. If the net serotonergic transmission returns to equilibrium after a sufficient amount of exposure to say, fluoxetine, how is it even working? Why doesn't it just poop out for everybody? It doesn't, though.Food for thought... Odd that I've never thought of that.
> This is not to say it *isn't* working, it's just always puzzled me, and up to this point I haven't seen a convincing explanation.
>
> Same goes with benzodiazepines. Excess stimulation of the GABA-ergic system --> downregulation or desensitization of benzodiazepine receptors (not sure which one it is) --> GABA-ergic transmission similar to baseline after sustained treatment. But what perplexes me (again!), is that the benzos continue to work for me - long after the "stress" has been relieved.
>
> So perhaps, they are somehow normalizing the equilibrium by placing this initial stress, with the subsequent compensatory efforts.
>
> This is just my idea of how it might work, but it seems logical / possible.Very good point! It seems very plausible.
> So, by "stress", what exactly do you mean, and what potential problems worry you (e.g. Nerve damage? Neoplasia?).
Well, as for the stress thing, see above... and I'm not worried about any problems really. I certainly don't have any specific concerns in mind (considering how little we know about these drugs, it would be quite hard to do so!). This whole thing was just a notion that popped into my head and kept nagging at me, so I had to ask! lol
> I ask these questions not cynically, but just to perhaps probe a bit more into what exactly you're concerned about.
>
> But I wouldn't worry about "sress" as long as you are feeling better, because we really don't have a clue what these drugs are doing (well, ok, we have *some* clue). That's why I am a big advocate of focusing on *symptoms*, and real life day-to-day functioning...things that we can measure (at least at this point).Very much agreed. Thanks so much for the insight! :-)
> Sorry for the rambly, blabbering form this post took. Haha.
Don't worry -- I am King of Unnecessary Verbiage, lol.
Michael
poster:Ame Sans Vie
thread:298512
URL: http://www.dr-bob.org/babble/20040109/msgs/299785.html