Intro to 5-HT1A Autoreceptor Desensitization

[@laynelurve7083]

You've done so much research on this. I hope you find a cure one day

[@janakignanan7793]

You have no idea how much this video means to me.. I'm writing an essay on depression and I really needed this. Thank you so much!

[@nadadenada319]

You forum saves my life, thanks

[@matthias66]

So hypothetically what you are saying in this video that the majority of the issues with, in regards to 5HT1A desensitization, is obviously the desensitization of the 5HT1A receptors (duh!), but more importantly, there is a dysfunction with the Go and Gi1 alpha subunit proteins. So you would have to correct the primary issue- the desensitization of the 5HT1A receptors, but also address the issue with the Go and Gi1 alpha subunit proteins. How do you think you would go about addressing the Go and Gi1 alpha subunits? Very good video. There has to be a way to fix this. PSSD sufferer here looking for answers and solutions, probably like the majority of the people who watch this video.

[@richikneogi1603]

Is this desensitization due to decoupling of G-proteins from their effectors (effector desensitization) rather than receptor endocytosis/degradation? I think you mentioned GABA-B receptors (which are localized in the somatodendritic compartment and axonal compartment) couple to the same G-proteins and are heterogeneously desensitized. I'm not sure if beta-arrestin is involved in 5HTr receptors (as it is with opioid and beta-adrenergic receptors), but perhaps decoupling via a traditional beta-arrestin mediated decoupling of G-protein from receptor or an ERK-mediated pathway may explain some of it. I suspect that MDMA's beneficial effect on depression (especially related to trauma) is due to global increases in serotonin release, bypassing traditional action-potential-mediated stimulation of 5HT release (i.e. by dumping 5HT into the synapse). This results in robust 5HT1A receptor signaling....

[@beinggreatest460]

Very informative .. thanks for the video 👌👌

[@JordanDinstrumentals]

Hi, I've been off ssris for over a year now and still can't get a strong erection like I used to. I took Escitalopram and first paxil during a six month period. I no longer have anxiety or depression regularly so that's not the cause and I still have sexual desire and can reach orgasm, I just can't get a strong enough erection for intercourse. Viagra doesn't work. Based on the info I've given you, is there any supplements you think could help me and also worsen me based on your research?

[@metaphorebbelaar6944]

Do you have your references listed somewhere? I see they are in the vid, but I mean like in an overview? It would be really helpful

[@sweetlaracroft4204]

Pssd ruined my life

[@godofallgodswithnoothernam920]

So the ligand gated ion channels of serotonin 5ht3a let's excessive potassium ions out preventing serotinergic signalling? Is that correct? Second question: the dorsal raphe nucleus exhibits increased serotinergic production yet the 5-HT autoreceptors are desensitised (or the G protein receptors serotonin acts on is decreased/ desensitised? Sorry for asking. Do please explain though. BTW if K+ is lacking due to hyperpermiable ion gated channels then would supplementing potassium sulphate chemical grade 99.9% pure be able to improve serotonin singling by increasingelectro-positivity inside the neurons electric gradient to threshold potential (of 70mv)? In your humble (non medical advice) opinion?

[@godofallgodswithnoothernam920]

How do i naturally unoccupy sert from the drug which preverts serotonin reuptake via sert. Study showed the drug sticks to the sert preventing its reuptake. Either way I just want sert sensitivity back. Any ideas. 5ht1a/5ht1c are where i want the agonism. Any thoughts if its natural I will do it.

[@godofallgodswithnoothernam920]

Sert gets synaptic cleft SA rexuces it enzymatically sends it to the neuron cell body axonal transport gets it the vessicle for more tight protien induces serotinergic signalling ? Right?

[@touch_master721]

Can receptors or will receptors get back to normal after stopping medication? And after how long time?

[@fdddff47]

Would desensitization accelerate with higher dosages ?

[@Soltanalipour]

what is the significance of gi/o, I thought they are always inhbitory?

[@javierantequeraquijano8542]

Someone please explain what is going on with the somatodendritic auto receptors. I do not understand the diagram, its like the axon is making a projection into its own cell body?

[@essany]

Are you still actively doing research?

[@ghostresearch7343]

Yes

[@essany]

@@ghostresearch7343 I'd like to talk to you sometime. If that's alright.

[@rbmma1883]

@WizardtheGreatest i treid rhodiola months b4 and it almost cured me for 1 day, then i try it months later, like 2 months ago, and it made me worse.

[@xxx-ly7jf]

when will there be a cure? 😞

[@jaycdp]

How come trintelix is causing nausea when it is a potent inhibitor of 5t3 receptar

[@pennwoman]

It’s not that simple. There are downstream effects on other neurotransmitters which can cause nausea despite the 5HT3 blockade. Blocking the 5HT3 receptors increases other neurotransmitters which can be causing the nausea. Ondansetron might help the nausea.

[@Seongbin99]

PSSD should be called something else. it is so much more than just numb genitle, so cruel to conclude it with such miniscule symptom compare to emotional blunting and anhefonia.

[@albergojason528]

Good job Gh0st. I have no doubt that the G proteins are affected by these drugs - however the long term disability that people experience from these drugs are also likely related to serotonin syndrome side effects - which can be more systemic in nature - i.e., causing nerve damage and toxicity in addition to the intracellular processes that you have described. Serotonin syndrome does not need to be acute in order to cause nerve damage, a low level form of this syndrome may be sufficient to damage the neurons and cause PSSD. Damaged neurons are located in the brain and the peripheral nervous system. Your hypothesis is very complex, but sometimes in science the most simple answer is the correct one. In this case, I believe you're over thinking this whole thing. The cause of PSSD is probably a combination of what you just described but mostly good old fashioned nerve damage.

[@9battlefieldheroes9]

@Conor 98 it is not written in the package leaflet. But pls don't become depressed because of it! You have a change to rise more awareness about it. Do research and inform the people/doctors around you! Take good care of yourself.

[@9battlefieldheroes9]

@Conor 98 Idk man, i'm very mad too. The only thing we can do is doing research and letting people know that SSRI's can be dangerous.

[@mscfplayervictor99]

Ngl dude sounds coked out explaining this but I heavily fuck w it thanks for uploading

[@elijhv]

PSSD