Dysregulated Dopamine Release From Serotonin Terminals Is The Prime Trigger Of Dyskinesia In The Rat

[Such_Saturation]

Dopamine released from 5-HT terminals is the cause of l-DOPA-induced dyskinesia in parkinsonian rats

 

[aguilaroja]

post 108687 Dopamine released from 5-HT terminals is the cause of l-DOPA-induced dyskinesia in parkinsonian rats

Nice find. Here's an article by the same lead author reviewing findings:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032899/

Serotonin System Implication in l-DOPA-Induced Dyskinesia: From Animal Models to Clinical Investigations
Manolo Carta,* and Elisabetta Tronci

"In line with this view, removal of serotonin neurons by selective toxin, or pharmacological silencing of their activity, produced complete suppression of LID (l-DOPA-induced dyskinesia) in animal models of Parkinson’s disease."

"In fact, silencing of serotonin neurons can be achieved by targeting the serotonin auto-receptors with selective agonists."

"Even more striking results were obtained using selective serotonin reuptake inhibitors (SSRIs), such as citalopram or fluoxetine..., which are known to exert their anti-depressant effect by increasing synaptic serotonin levels. In these studies, the authors observed complete suppression of LID at relatively low doses of drugs, while a 5-HT1 receptor antagonist appeared to counteract this effect, suggesting that increased activation of serotonin auto-receptors is involved in the mechanisms of the anti-dyskinetic effect of SSRIs in parkinsonian rats."

haidut and others have discussed the nuances of speaking beyond the simple agonism/antagonism of serotonin "receptors", for instance:

https://www.raypeatforum.com/forum/viewtopic.php?t=6740
"Peat said that "agonizing" certain receptors like 5-HT1 actually has a negative feedback mechanism on serotonin release so it leads to reduced synthesis of serotonin and increase in dopamine. The Wikipedia page sort of backs up this claim of Peat by saying agonizing the 5-HT1 receptor triggers dopamine release, hence the effects of agonists like lisuride and bromocriptine on Parkinson's and schizophrenia.
http://en.wikipedia.org/wiki/5-HT1A_receptor"

 

[Such_Saturation]

Which is why cyproheptadine gives me restless legs

 

[Such_Saturation]

Maybe this is how LSD works, and I'm pretty sure cyproheptadine can block LSD trips.

 

[Nighteyes]

post 108704 Maybe this is how LSD works, and I'm pretty sure cyproheptadine can block LSD trips.

I was under the impression that Cyproheptadine was actually derived from LSD and that both have similar effects, one of them being bringing down serotonin (which is what brings the vivid colours etc. on LSD).

 

[Such_Saturation]

post 108728

post 108704 Maybe this is how LSD works, and I'm pretty sure cyproheptadine can block LSD trips.

I was under the impression that Cyproheptadine was actually derived from LSD and that both have similar effects, one of them being bringing down serotonin (which is what brings the vivid colours etc. on LSD).

Yes it is interesting, but I think the traditional ligand theory starts to break down here, and I think Ray Peat would say that molecules don't really differ quantitatively in their action as much as qualitatively. For the cell, each substance is a story on its own and blocking the serotonin system is a complex matter because it is engrained within us and it used to need to accomplish many functions. Look at this:

LSD exhibits functional selectivity at the 5-HT2A and 5HT2C receptors in that it activates the signal transduction enzyme phospholipase A2 instead of activating the enzyme phospholipase C as the endogenous ligand serotonin does.

 

[Giraffe]

post 108703 Which is why cyproheptadine gives me restless legs

Damn, does it? I wondered about this. German Wikipedia writes that up to 25% of the MIrtazapine users get RLS; English Wikipedia writes less than 0.1% of the users get restless legs.

Such_, is this side-effect dose dependant for you?

 

[Such_Saturation]

post 108896

post 108703 Which is why cyproheptadine gives me restless legs

Damn, does it? I wondered about this. German Wikipedia writes that up to 25% of the MIrtazapine users get RLS; English Wikipedia writes less than 0.1% of the users get restless legs.

Such_, is this side-effect dose dependant for you?

Yes same as for anhedonia.

 

[DaveFoster]

Yes it is interesting, but I think the traditional ligand theory starts to break down here, and I think Ray Peat would say that molecules don't really differ quantitatively in their action as much as qualitatively. For the cell, each substance is a story on its own and blocking the serotonin system is a complex matter because it is engrained within us and it used to need to accomplish many functions. Look at this:

LSD exhibits functional selectivity at the 5-HT2A and 5HT2C receptors in that it activates the signal transduction enzyme phospholipase A2 instead of activating the enzyme phospholipase C as the endogenous ligand serotonin does.

I don't know what this means, but it sounds cool. LSD good, serotonin bad.

 

[Giraffe]

post 108975 Yes same as for anhedonia.

Do you mean you get anhedonia from cypro? At what dosage do you get side-effects such as anhedonia and restless legs?

 

[Such_Saturation]

post 108989

post 108975 Yes same as for anhedonia.

Do you mean you get anhedonia from cypro? At what dosage do you get side-effects such as anhedonia and restless legs?

viewtopic.php?f=99&t=8299&p=106687

 

[Giraffe]

Such_, thanks! I don't know why I didn't find that topic.

 

[Such_Saturation]

 

[messtafarian]

This is confusing to me. When I was tested for catecholamines I had slightly high serum dopamine and I had started taking cypro. I tried to figure out what it meant but there's not much to be found about serum dopamine, only dopamine in the brain. I take a lot of cypro, it's really really helped me -- but I wonder if it then downregulates dopamine sensitivity.