How does serotonin inhibit sexuality exactly?

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taarn
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How does serotonin inhibit sexuality exactly?

Unread post by taarn »

It's widely known that serotonin has an inhibitory effect on sexuality. I've read many things but still don't know how this exactly happens, which receptor subtypes are mostly involved and what downstream events of their activation result in that.

Does anybody know how serotonin inhibits sexuality?

I'm linking Mesolimbo's thread cause it's a good starter and modulation of glutamate neurotransmission is very likely involved. But it would be good to know more about this phenomenon.
viewtopic.php?f=22&t=2754

Unfortunately I'm scarce on time recently but I'm planning to research this area more thoroughly and update the topic. Contributions in the form of your own thoughts or linking research material are very welcomed.
taarn
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Re: How does serotonin inhibit sexuality exactly?

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reserved
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Delfador
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Re: How does serotonin inhibit sexuality exactly?

Unread post by Delfador »

Serotonine itself does not inhibit sexuality...in normal people serotonine is mostly pro-sexual.
I know my opinion might upset some old members but it shouldn't. I'm just posting it as a disclaimer for forum newbies who usually hop on a hopeless crusade against serotonine itself either by means of serotonine antagonism or serotonine depletion.

To answer your question, overactivity of 5ht2 subtype receptors inhibits dopamine firing in the nucleus accumbens and striatum which globally means lower libido.

But it has been proven countless of times that this is not the reason behind pssd (although 5ht2c might be responsible of low libido DURING ssri treatment).
You can take all the serotonine 5ht2c antagonists of the world and you wont feel much better...you will only feel looow, irritated and miserable.
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Meso
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Re: How does serotonin inhibit sexuality exactly?

Unread post by Meso »

Serotonin inhibits libido through 5 main mechanisms:
1- Increasing prolactin release: many serotonin subtypes (5HT1A "postsynaptic-only", 5HT2, 5HT3, 5HT4) increase prolactin release.

2- Elevation of beta-endorphin: mainly postsynaptic 5HT1A. Beta-endorphin interferes with sex hormones drastically, blunting libido, as well as increasing prolactin. However, mu agonism is crucial for orgasmic intensity.

3- TONIC dopamine firing inhibition: 5HT2 receptors are modulators for dopamine phasic vs tonic release. Tonic firing is extremely important for libido, whereas phasic firing is much less involved in it. That said, 5HT2 receptors are largely inhibitory to sexual function in lieu of their prolactin increasing effect and reduction of tonic dopaminergic release.

4- Nitric oxide inhibition: 5-HT1B/1D and 5HT2B receptors are involved in nitric oxide production. With chronic increase in 5HT, these autoreceptors (1B/1D) become desensitized and you end up with less nitric oxide production.

5- Inhibition of the NMDA-cGMP pathway by 5HT1A and 5HT2C receptors activation.

Sorry for not providing studies. I've written these off the top of my head, but feel free to double check on/ Pubmed.
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iull1k
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Re: How does serotonin inhibit sexuality exactly?

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Do not forget about AR downregulation, Neurosteroidal and Androgen Modulation.
Blueturtle
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Re: How does serotonin inhibit sexuality exactly?

Unread post by Blueturtle »

Mesolimbo wrote:Serotonin inhibits libido through 5 main mechanisms:
1- Increasing prolactin release: many serotonin subtypes (5HT1A "postsynaptic-only", 5HT2, 5HT3, 5HT4) increase prolactin release.

2- Elevation of beta-endorphin: mainly postsynaptic 5HT1A. Beta-endorphin interferes with sex hormones drastically, blunting libido, as well as increasing prolactin. However, mu agonism is crucial for orgasmic intensity.

3- TONIC dopamine firing inhibition: 5HT2 receptors are modulators for dopamine phasic vs tonic release. Tonic firing is extremely important for libido, whereas phasic firing is much less involved in it. That said, 5HT2 receptors are largely inhibitory to sexual function in lieu of their prolactin increasing effect and reduction of tonic dopaminergic release.

4- Nitric oxide inhibition: 5-HT1B/1D and 5HT2B receptors are involved in nitric oxide production. With chronic increase in 5HT, these autoreceptors (1B/1D) become desensitized and you end up with less nitric oxide production.

5- Inhibition of the NMDA-cGMP pathway by 5HT1A and 5HT2C receptors activation.

Sorry for not providing studies. I've written these off the top of my head, but feel free to double check on/ Pubmed.

Jesus Christ.

Reading all of that freaks me out, it’s like where do I start? So SSRIS LITERALLY EFFECT ALL OF the systems important for sexuality? It’s so overwhelming, it’s like I don’t know where to start in terms of treatment.
PSSD from citalopram.
Took it Winter 2012-Summer 2016
Cut cold turkey. Symptoms include genital anesthesia, ejaculatory anhedonia, low libido, Burning/tingling genital pain.
My story: http://www.pssdforum.com/viewtopic.php?f=14&t=2536
taarn
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Re: How does serotonin inhibit sexuality exactly?

Unread post by taarn »

Mesolimbo wrote:Serotonin inhibits libido through 5 main mechanisms:
1- Increasing prolactin release: many serotonin subtypes (5HT1A "postsynaptic-only", 5HT2, 5HT3, 5HT4) increase prolactin release.

2- Elevation of beta-endorphin: mainly postsynaptic 5HT1A. Beta-endorphin interferes with sex hormones drastically, blunting libido, as well as increasing prolactin. However, mu agonism is crucial for orgasmic intensity.

3- TONIC dopamine firing inhibition: 5HT2 receptors are modulators for dopamine phasic vs tonic release. Tonic firing is extremely important for libido, whereas phasic firing is much less involved in it. That said, 5HT2 receptors are largely inhibitory to sexual function in lieu of their prolactin increasing effect and reduction of tonic dopaminergic release.

4- Nitric oxide inhibition: 5-HT1B/1D and 5HT2B receptors are involved in nitric oxide production. With chronic increase in 5HT, these autoreceptors (1B/1D) become desensitized and you end up with less nitric oxide production.

5- Inhibition of the NMDA-cGMP pathway by 5HT1A and 5HT2C receptors activation.

Sorry for not providing studies. I've written these off the top of my head, but feel free to double check on/ Pubmed.
Thanks, it's a good starter for my research in this topic.
Blueturtle wrote:Jesus Christ.

Reading all of that freaks me out, it’s like where do I start? So SSRIS LITERALLY EFFECT ALL OF the systems important for sexuality? It’s so overwhelming, it’s like I don’t know where to start in terms of treatment.
SSRIs are the worst, but I don't think that it applies only to them. Everything that messes with serotonin is a potential danger to your sexuality, especially antidepressants with potent SRI properties. I would avoid 5-HTP, and serotonergic drugs like MDMA and others.. Some psychedelics with serotonergic properties seems less dangerous in this regard.

It's hard to go after each subsystem with disturbances, try to amplify main prosexual pathways.
Fix any hormone imbalances, good hormonal environment is the basis for recovery. Then dopaminergics, cholinergics and probably anti-serotonergics could be helpful. You're better if you combine them but the best would be to tailor to your symptoms.
Blueturtle
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Re: How does serotonin inhibit sexuality exactly?

Unread post by Blueturtle »

@ Taarn

Yes that seems to be the case, I have heard of people getting PSSD like symptoms from 5-htp and MDMA.


That makes sense try to boost the prosexual stuff rather then try to make your system “less bad” for sex.

Wellbutrin gave me a 40% recovery I’d say I responded more to sexual stimuli and actually felt pleasure but it was still far from what I remembered and the effect wore off.

Have you had success with a particular regiment taarn?
PSSD from citalopram.
Took it Winter 2012-Summer 2016
Cut cold turkey. Symptoms include genital anesthesia, ejaculatory anhedonia, low libido, Burning/tingling genital pain.
My story: http://www.pssdforum.com/viewtopic.php?f=14&t=2536
taarn
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Joined: Thu Dec 27, 2018 12:38 pm
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Re: How does serotonin inhibit sexuality exactly?

Unread post by taarn »

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Last edited by taarn on Sun Apr 21, 2019 10:14 am, edited 1 time in total.
taarn
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Re: How does serotonin inhibit sexuality exactly?

Unread post by taarn »

Blueturtle wrote:@ Taarn

Yes that seems to be the case, I have heard of people getting PSSD like symptoms from 5-htp and MDMA.


That makes sense try to boost the prosexual stuff rather then try to make your system “less bad” for sex.

Wellbutrin gave me a 40% recovery I’d say I responded more to sexual stimuli and actually felt pleasure but it was still far from what I remembered and the effect wore off.

Have you had success with a particular regiment taarn?
I've tried many things so far but haven't found a regimen that works sustainably to treat sexual dysfunction. Wellbutrin was the best for for sexual dysfunction symptoms, it also helped with emotions. But I only retained the emotional improvements. Dopamine agonists were totally useless btw.

BPC-157 and CDP-Choline were good for cognitive issues and brain fog, I would say 100% relief in this regard. BPC also helped with my mood.

Ipamorelin + Mod-GRF 1-29 helped with sleep and regeneration. My sleep is quite acceptable now. Although anxiety and OCD disappeared when I got PSSD, my sleep was far from perfect and I happened to have issues.
I'm also taking Forskolin daily, I feel it gives me more energy.

These were the most helpful to date, but I will create a detailed log thread soon.
I'm still waiting for meds and some chemicals to arrive, I still have to do a lot of experimenting. I will also meet my psych soon and also a neurologist so I will try to get some prescriptions.

What I think (and hope) to work as a sustainable treatment regimen is the following:
1.) An acetylcholinesterase inhibitor: Donepezil, Rivastigmine or Galantamine
2.) Something to boost tonic dopamine: Rasagiline or Amantadine
3.) Something anti-serotonergic: Metergoline or Ketanserin

I'm still thinking on how to avoid tolerance or desensitization. Likely I will incorporate some Memantine but it's also possible Amantadine don't have such issues with tolerance. I'm also thinking about adding NAC to the regimen but I'm afraid of the glutamate transporter upregulation, I have to research that a bit more.
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