8 replies to this topic

[the_apollo]

Venlafaxine is said by many to cause memory dysfunction in forms of less ability to retain information(form memories), less ability to remember
things and in some cases also impairing working memory.

Things like that worries me a little since my drrr has put me on Venlafaxine for depression, which i kind.. of have, it's more of anxiety and irritability,
but anyway, i started to search for why it may be that the drug can cause memory impairment, (my memory is already kind of bad, really dont want to impair it)
i found a study saying that in rats treated chronically with venlafaxine, there was a "reduced signal transduction by 5HT4 receptors"
 (possibly caused by what the study stated as "functional desensitization",
the study also states that venlafaxine also decreased the density of 5HT4 receptor(s) in striatal/basal ganglia and hippocampal areas.


I like my 5HT4 receptors. I like acetylcholine, so what i had in mind to ask is: Is there any way/s to increase 5HT4 receptor density and/or signal transduction,
and is there any way to reverse venlafaxine-induced decrease in 5HT4 receptor activity ?

Sure would be nice if there was an 5HT4 positive allosteric modulator or anything like that..

 

 

Treatment with a high dose (40 mg·kg⁻¹) of venlafaxine did not alter 5-HT₄ mRNA expression, but decreased the density of 5-HT₄ receptors in caudate-putamen (% reduction = 26 ± 6), hippocampus (% reduction = 39 ± 7 and 39 ± 8 for CA1 and CA3 respectively) and substantia nigra (% reduction = 49 ± 5)

http://www.ncbi.nlm....les/PMC2990165/

Edited by the_apollo, 29 May 2014 - 12:21 AM.

[blood]

According to this study, "failing memory" was experienced at a significantly higher rate in those receiving "high dose" (>375 mg/day) versus "low dose" (<375 mg/day) venlafaxine.

What dose are you on?

FWIW I haven't experienced memory problems @ 75 mg/day or 150 mg/day.

Edited by blood, 29 May 2014 - 07:37 AM.

[Flex]

Regarding Your link:

 

..Our data indicate a functional desensitization of 5-HT₄ receptors after chronic venlafaxine, similar to that observed after treatment with the classical selective inhibitors of 5-HT reuptake...

 

I guess therefore that many people experienced the same effects

and that the alteration should be supposedly reversible on its self.

 

Btw: I´ve taken a few years ago also Vellafaxine for a couple of months, but didnt experienced memory impairments.

 

 

[the_apollo]

According to this study, "failing memory" was experienced at a significantly higher rate in those receiving "high dose" (>375 mg/day) versus "low dose" (<375 mg/day) venlafaxine.

What dose are you on?

FWIW I haven't experienced memory problems @ 75 mg/day or 150 mg/day.

 

I am currently at 75mg per day, but since it's possible that my dosage will be increased i want to have this possible problem fixed, i mean, if there is any way(s) to restore 5HT4 receptor function, why not?

Why not increase 5HT4 receptor function /and density that may be decreased with venlafaxine treatment.

[Flex]

Cant help You with that. But would be interrested as well,

if there is something that changes the density.

[blood]

Why not increase 5HT4 receptor function /and density that may be decreased with venlafaxine treatment.

 

 

Questions

 

- Is it clear that reduced 5HT4 density or signal transduction is a bad thing? Maybe it's actually a good thing, or a neutral thing, with respect to mood?

 

- What is the link if any between 5HT4 signalling and memory?

 

-Does altered 5HT4 signalling even occur in people on typical doses of venlafaxine (as opposed to in rts on very high doses of venlafaxine)?

[focus83]

Megadosing Inositol purportedly (re)sensitizes 5HT receptors.

[the_apollo]

 

Why not increase 5HT4 receptor function /and density that may be decreased with venlafaxine treatment.

 

 

Questions

 

- Is it clear that reduced 5HT4 density or signal transduction is a bad thing? Maybe it's actually a good thing, or a neutral thing, with respect to mood?

 

- What is the link if any between 5HT4 signalling and memory?

 

-Does altered 5HT4 signalling even occur in people on typical doses of venlafaxine (as opposed to in rts on very high doses of venlafaxine)?

 

 

 

 

In respect to mood, i dont know, but i do know that Acetylcholine is involved with memory function, and cognition when related to frontoparietal areas.

 

5-HT4 receptor stimulation facilitates acetylcholine release in rat frontal cortex

http://www.ncbi.nlm..../pubmed/7919171

[Area-1255]

 

Why not increase 5HT4 receptor function /and density that may be decreased with venlafaxine treatment.

 

 

Questions

 

- Is it clear that reduced 5HT4 density or signal transduction is a bad thing? Maybe it's actually a good thing, or a neutral thing, with respect to mood?

 

- What is the link if any between 5HT4 signalling and memory?

 

-Does altered 5HT4 signalling even occur in people on typical doses of venlafaxine (as opposed to in rts on very high doses of venlafaxine)?

 

5-HT4 receptors are stimulatory and contractile, especially in certain regions of the brain. They do have an inotropic effect, and are G-protein coupled (and thus increases cAMP - cyclic AMP) - they are one of the more potent serotonin receptors in regard to this stimulant effect.

 

http://www.pharmacor...rotonin_2_2.php

 

However I wouldn't be overly concerned about 5-HT4 desensitization of ALL effects, keep in mind 5-HT4 also has a prominent effect on hormones, including prolactin secretion.

 

http://www.rainbow.c...lactin-release/

 

http://www.ncbi.nlm....pubmed/17122082

 

http://www.ncbi.nlm..../pubmed/8738578

 

Besides, there are ALOT of other receptors in the body / CNS / Brain that release cAMP - 5-HT4's are relatively insignificant (even though of the serotonin class they are "potent") - if anything, you should worried about cAMP DECREASES while on SSRI's - considering the amount of serotonin receptors and overall effects of serotonin have a larger tendency to decrease cAMP levels, especially over time.

5-HT1A,1B,1D, 

5-HT5A all inhibit adenylyl cyclase - and to an extent generally stronger than the increase one would see with serotonin at 5-HT7 and and 5-HT4 etc

 

 

I would therefore see (and from experience) that methods to reverse SSRI induced cognitive dysfunction would include (generally) increase cAMP (such as with beta-adrenergic agonists, geranamine, or forskolin).

 

http://www.uptodate....ase/abstract/45

 

http://www.biomed.ca...df/60/60_15.pdf

 

http://books.google....riction&f=false

 

http://www.pharmacor...rotonin_2_2.php