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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by NKP on October 6, 2021, at 4:15:09
LTP = long-term potentiation
My understanding is that LTP is the strengthening of frequently used neural pathways.
Venlafaxine inhibits LTP in the hippocampus:
https://pubmed.ncbi.nlm.nih.gov/19464349/
What are the consequences of this? For example, would this not reduce neural plasticity?
Posted by undopaminergic on October 6, 2021, at 11:37:52
In reply to What are the consequences of inhibiting LTP?, posted by NKP on October 6, 2021, at 4:15:09
> LTP = long-term potentiation
>
> My understanding is that LTP is the strengthening of frequently used neural pathways.
>
> Venlafaxine inhibits LTP in the hippocampus:
>
> https://pubmed.ncbi.nlm.nih.gov/19464349/
>
> What are the consequences of this? For example, would this not reduce neural plasticity?
>I would expect learning impairment from inhibiting LTP. On the other hand, maybe it could help keep frequently used "depressive" neural pathways from getting stronger (I'm thinking especially of rumination).
-undopaminergic
Posted by linkadge on October 8, 2021, at 18:16:33
In reply to Re: What are the consequences of inhibiting LTP?, posted by undopaminergic on October 6, 2021, at 11:37:52
It is interesting because I have read studies suggesting that venlafaxine both inhibits LTP and increases neurogenesis. I don't know the clinical significance of inhibiting LTP as venlafaxine has been shown to improve memory in a number of studies:
https://pubmed.ncbi.nlm.nih.gov/12866715/
https://pubmed.ncbi.nlm.nih.gov/16696296/
https://pubmed.ncbi.nlm.nih.gov/15819387/
(and many others)Venlafaxine has some antioxidant mechanisms as well as an ability to reduce overall brain inflammation. The effect in a 'depressed' brain may be very different from a 'normal' brain. I remember reading some studies that (in mice) depression like behavior is actually associated with an intensification of memory processes and that wiping out memory actually improved behavior.
My hunch is that venlafaxine tips the balance between acetylcholine and monoamines in the hippocampus. Acetylcholine can strengthen LTP but it can also induce depression. Administering muscarinic (acetylcholine) blockers in the hippocampus reduces depression but also inhibits LTP. In the depressed brain there may be an abundance of acetylcholine relative to monoamines in the hippocamps. As undopaminergic suggests this could lead to the induction of rumination (old processes) and inability to engage in new behaviors. Venlafaxine might inhibit this process, thus reducing the strengthening of existing (ruminative) memories.
Overall, I wouldn't worry about it too much. I don't think this is indicative of permanent damage as generally venlafaxine is seen as neuroprotective. There may be a temporary shift in memory processes that would likely revert once the drug is discontinued.
For me, the best antidepressants completely wipe my memory out. For me, weed works when nothing else does, and I feel the best when I can barely remember my own name.
Linkadge
Posted by undopaminergic on October 11, 2021, at 15:29:53
In reply to Re: What are the consequences of inhibiting LTP?, posted by linkadge on October 8, 2021, at 18:16:33
> It is interesting because I have read studies suggesting that venlafaxine both inhibits LTP and increases neurogenesis. I don't know the clinical significance of inhibiting LTP as venlafaxine has been shown to improve memory in a number of studies:
>You seem to know a lot about venlafaxine. Have you tried it yourself?
>
> My hunch is that venlafaxine tips the balance between acetylcholine and monoamines in the hippocampus. Acetylcholine can strengthen LTP but it can also induce depression.
>Yes. I read about a hypercholinergic mouse model of depression many years ago, but when, recently, I tried to look into it again, I could not find anything.
I think I may be hypercholinergic. My pupils are always small and I seem to be undersensitive to anticholinergics.
> For me, the best antidepressants completely wipe my memory out. For me, weed works when nothing else does, and I feel the best when I can barely remember my own name.
>
> LinkadgeHave you tried anticholinergics? I seem to recall that you had belladonna extract?
-undopaminergic
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