5-ht theory and steroidogenesis [Coraggio's corner]

[Foxx]

I'm Zero, this is my second (old) account, I'm waiting for another ban. First and main reason is that this forum simply scares, makes me stressed out and ultimately restrains from recovery and recovery means forgetfullness. Second I believe you won't find any cure and I'm a bit of tired of attempts to reinvent a wheel over and over again by some.. Moreover nobody is eager to make a trial with silly Bacopa, or Forskolin. I have a medical background too, but it doesn't matter much, wise self-experiments and some eagerness to tinker in researches matter.

I've presented I believe a solid research about SERT according to which g-protein desensitisation doesn't even exist (can't be so sure though). After 3 months uncoupled from g-proteins 5-HT1A receptors returned to normal in SERT+/+ animals, however SERT knocked out(-/-) mice present 5-ht1A persistent desensitisation. MDMA seems to be a "turbo-ssri". Bacopa helped with MDMA damage (one case most likely), thats why it's promising, another interesting compound is Forskolin.

Some hints:

In these cells, the protein kinase C activator β-PMA caused a time-dependent reduction in 5-HT uptake capacity (V max) after acute application and a reduction in SERT-mediated currents.

MDMA regulates serotonin transporter function via a Protein kinase C dependent mechanism

Reduction in the density and expression, but not G-protein coupling, of serotonin receptors (5-HT1A) in 5-HT transporter knock-out mice: gender and brain region differences.

Raphe-mediated signals control the hippocampal response to SRI antidepressants via miR-16

Nobody wants to dig further into that stuff, It's about PKC, heterodimerization, opioids, etc, etc.. I'm severely derealized and looking further into this is unhealthy for me, so I've abandoned that stuff. Also I'm ashamed that nobody even did reply, so I guess recognized this as not so important. Don't want to sound as an attention whore (maybe slightly I am), but this is the stuff, loss of the SERT is real and it would be HIGHLY DESIRED for everyone to bring this stuff somewhat up. Because of "Collaborative Research" and possible further outcome. I'd love to be surprised by someone.

http://www.pssdforum.com/viewtopic.php?f=10&t=694
I mean sections especially below "possible treatment".

interesting info btw:
http://jeffreydachmd.com/clomid-for-men ... tosterone/

I've tried all that stuff like Bacopa (days), Berberine, Evodiamine, Rhodiola, etc One thing is upregulating SERT "on demand", second is long term upregulation. Overall it's not so simple. Sex steroids are heavily underestimated here, same as 5-HT2A/2C properties and overall neuro-endocrine profile. Although Area is a psycho he's right about that.

Steroids upregulate SERT, but I believe their therapeutic properties extend far beyond, I'm too tired it's all the same here, always snack, never dinner.

Personally I give up. One of my last posts I hope. Thinking about own brain as flawed makes one flawed.

[forexworld12]

One thing that I've wondered about SERT is that maybe the desensitization is only staying because SERT is down-regulated.

I conjecture that your statement is the truth.

[forexworld12]

The more that I think about this...the more that it makes sense.

http://www.jneurosci.org/content/19/23/10494.full.pdf

"Based on these results, it appears that the SERT is
downregulated by chronic administration of SSRIs but not other
types of antidepressants; furthermore, the downregulation is
not caused by decreases in SERT gene expression."

IF this continued after drug treatment, THEN desensitization would continue indefinitely. I still need to think over the regulators of G-Protein stuff, but in theory I think that this could be a result of the increased 5HT, which COULD be from decreased SERT expression.

I liked the article that I posted above, but had a few comments on it

- They addressed what they think are errors in older studies showing no change in SERT due to SSRIs, but it's still a bit unnerving that there is so much debate over it (this is also 17 years old and a lot could have changed - I haven't read recent literature).

- They mention an MAOI that they used that actually INCREASED SERT levels. That brings to mind SJW, which is a natural MAOI. I know that user beetlebum recovered after it. But they also talk about how other factors in the drug could be at play.

- I don't like how they measured SERT action in the Hippocampus, and then SERT expression in the DRN, and then concluded that SERT mRNA isn't to blame. They are measuring from 2 different brain areas and I don't think that's a fair assumption to make: that SERT changes are global. Basically, they check for function in the Hippocampus, and then expression in the DRN.

- Brings up the point that post-translational regulation could play a role.

Yeah, but I want to say my doubts still unsolved. Maybe you can find an answer. My doubts are: 1)why so many people doesn' t improve after long term therapy of berberine if berberin can upragulates SERT. 2) maybe SERT expression is always strong linked with Thryptophan hydroxylase like bacopa. I' ve read about correlation between SERT phenotype and stress coping behavior. Good presence of SERT is linked with good stress coping and low SERT expression the opposite. This goes against what expected by researchers. Also I' ve found evodiamine can improve neurotransmitter levels of NA,DA and serotonin. It presents MAOI activity too.

A herb is not designed in such a way to counter and restore a chemically induced down-regulation

[Ghost]

I'm Zero, this is my second (old) account, I'm waiting for another ban.

Let me get this straight...

You think that you have a good theory to PSSD, but you want me to ban your account and have other people figure it out for you?

I've been trying really hard to start a new research group, and hope that the scientific minds here stick around to help me do it.

I never would have slightly believed a SERT theory until after I had learned about g-proteins, because only then did I realize that they could be connected.

My job here is to make the forum useful for all. So I'm always open to suggestions as to how to do that.

Ghost

[Foxx]

I'm Zero, this is my second (old) account, I'm waiting for another ban.

Let me get this straight...

You think that you have a good theory to PSSD, but you want me to ban your account and have other people figure it out for you?

I've been trying really hard to start a new research group, and hope that the scientific minds here stick around to help me do it.

I never would have slightly believed a SERT theory until after I had learned about g-proteins, because only then did I realize that they could be connected.

My job here is to make the forum useful for all. So I'm always open to suggestions as to how to do that.

Ghost

Lurking, reading, researching about (my own) pssd is damaging, kind of learning about snow with a torch. Hovering around pssd alone is very stressful and harmful. My baseline seems to be good enough to forget about this forum and I'm looking forward into it. Overall it's a personal stuff, kind of "recovery step 9 - unsubscribe by perma-ban". It's nothing about this forum per se, however I don't like everything. Forum has to exist, I'd be probably dead without this community and 5-HT1A stuff btw.

I didn't wanted to bury SERT theory because I feel it's a good stuff and heavily overlooked, could be connected with g-proteins, nobody knows. I just want other people to push that theory further/or disprove. I know roughly my way out, I don't desperately need an antidote. I'm here since early 2015, now it's time to say farewell - because thoughts create reality and I don't want to think about pssd anymore.

[Coraggio]

Ok, I respect you and your idea. I've everything awesome in life until the pssd. I would stay away from this nightmare but this is all made by our mad world and now we are fucked. If you are feeling good with your improvement fixed by mianserine and ginko I' m glad for you. I hope here door still remain open for you. If you can tell us your story and details of your improvements before say goodbye

[Foxx]

I'm on survivingantidepressants as "Zero", there's my log. I'm kind of leaving like I said, but not off this planet yet.

[sjv16477]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670606/

SSRI in very low dose (10-50 fold less then the one required to inhibit SERT) acts as rapid and potent brain steroid synthesis stimulator.

[GIXXER]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670606/

SSRI in very low dose (10-50 fold less then the one required to inhibit SERT) acts as rapid and potent brain steroid synthesis stimulator.

Is that good or bad?

[sjv16477]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670606/

SSRI in very low dose (10-50 fold less then the one required to inhibit SERT) acts as rapid and potent brain steroid synthesis stimulator.

Is that good or bad?

Someone says that pssd is caused by an impaired steroidogenesis, then this may be good.