Serotonergic 5-HT2A receptor stimulation induces steroid 5alpha-reductase gene expression

[iull1k]

Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of depressive mood disorders and well known to inhibit the reuptake of neurotransmitter serotonin into nerve terminals. Thus, it seems conceivable that these drugs may induce the outflow of serotonin from the synapse as a consequence of inhibiting the reuptake, resulting in the stimulation of glial cells surrounding nerve terminals. On this hypothesis, the effect of serotonin on steroid 5alpha-reductase type 1 (5alpha-R) gene expression in rat C6 glioma cells was examined as one of the in vitro model experiments for investigating the indirect influence of SSRIs on glial cells. Serotonin elevated 5alpha-R mRNA and protein levels through the stimulation of serotonin 5-HT2A receptors, and also elevated Egr-1 mRNA and protein levels prior to 5alpha-R gene expression in the glioma cells. Furthermore, serotonin failed to significantly increase 5alpha-R mRNA levels in the cells preloaded with the antisense oligodeoxynucleotide targeted on Egr-1 gene. These results indicate that serotonin may stimulate 5alpha-R gene expression via transcription factor Egr-1 in glial cells, thus suggesting that serotonin flowing out of the serotonergic synapse may be implicated in SSRI-induced changes in neurosteroid metabolism in brain.

https://www.ncbi.nlm.nih.gov/pubmed/15936112

[Meso]

Nice find.

Inositol and SJW can upregulate 5HT2A. Panax Ginseng is a non-psychedelic 5HT2A agonist. However, keep in mind that 5HT2 stimulation increases prolactin and decreases dopamine firing. (But also increases oxytocin release --> mu opioid sensitivity)

[Meso]

This can also be a link between Accutane, PFS, and PSSD. Accutane upregulates the presynaptic 5HT1A and SERT mRNA expression. This can cause drastically less activation of 5HT2A and downregulation of 5alpha-reductase mRNA expression.

I've discovered recently that my type of PSSD is due to supersensitivity of presynaptic 5HT1A receptors. Full agonists also give me extreme sexual dysfunction and I'm trying Vortioxetine to downregulate these receptors. 5HT2A could be the link for my reaction.

I also remember that Panax Ginseng (Red Korean Ginseng) can restore my libido somewhat. It's a non-psychedelic 5HT2A agonist, IIRC. Anyway, great find man.

[taarn]

This can also be a link between Accutane, PFS, and PSSD. Accutane upregulates the presynaptic 5HT1A and SERT mRNA expression. This can cause drastically less activation of 5HT2A and downregulation of 5alpha-reductase mRNA expression.

I've discovered recently that my type of PSSD is due to supersensitivity of presynaptic 5HT1A receptors. Full agonists also give me extreme sexual dysfunction and I'm trying Vortioxetine to downregulate these receptors. 5HT2A could be the link for my reaction.

I also remember that Panax Ginseng (Red Korean Ginseng) can restore my libido somewhat. It's a non-psychedelic 5HT2A agonist, IIRC. Anyway, great find man.

Then does this imply that serotonin is essential to sexual function? What about the studies which show increased sexuality after serotonin depletion? (Or in genetically modified animals lacking serotonin)

[Meso]

Then does this imply that serotonin is essential to sexual function? What about the studies which show increased sexuality after serotonin depletion? (Or in genetically modified animals lacking serotonin)

Some serotonin receptors are pro-sexual, while others are antisexual. Even, some receptors enhance different aspect of sexuality where they enhance erections but blunt ejaculation and vice-versa. It comes down to the genetic make up of a person. SSRIs can even increase libido in some people.

Some of the studies are also faulty. For example, it has been found that serotonin deficiency in rats change their sexual preference to a homosexual tendency (so they shouldn't have tested for male-female mounting), while other studies found that MDMA-induced serotonin depletion only caused lower sexual function in 50% of the rats.

It also comes down to testosterone/dopamine/prolactin levels and how sensitive a person is to changes in them. To complicate things further, lower serotonin release (via increased presynaptic 5HT1A density) would cause depression and dysfunction of the mesolimbic pathway -- which can cause sexual dysfunction by its own right in the genetically susceptible.

[ErgogenicHealth]

This can also be a link between Accutane, PFS, and PSSD. Accutane upregulates the presynaptic 5HT1A and SERT mRNA expression. This can cause drastically less activation of 5HT2A and downregulation of 5alpha-reductase mRNA expression.

I've discovered recently that my type of PSSD is due to supersensitivity of presynaptic 5HT1A receptors. Full agonists also give me extreme sexual dysfunction and I'm trying Vortioxetine to downregulate these receptors. 5HT2A could be the link for my reaction.

I also remember that Panax Ginseng (Red Korean Ginseng) can restore my libido somewhat. It's a non-psychedelic 5HT2A agonist, IIRC. Anyway, great find man.

Curious to know how you have responded to low dose cyproheptadine?

[ErgogenicHealth]

This can also be a link between Accutane, PFS, and PSSD. Accutane upregulates the presynaptic 5HT1A and SERT mRNA expression. This can cause drastically less activation of 5HT2A and downregulation of 5alpha-reductase mRNA expression.

I've discovered recently that my type of PSSD is due to supersensitivity of presynaptic 5HT1A receptors. Full agonists also give me extreme sexual dysfunction and I'm trying Vortioxetine to downregulate these receptors. 5HT2A could be the link for my reaction.

I also remember that Panax Ginseng (Red Korean Ginseng) can restore my libido somewhat. It's a non-psychedelic 5HT2A agonist, IIRC. Anyway, great find man.

What happens when you try Cyproheptadine?!

[fellow1]

could anyone suggest presynaptic 5ht1a antagonist ?