The DOPAMINE DOWN-REGULATION - AND HOW IT PLAYS A MAJOR ROLE IN PSSD

Jason,has often talked about common and complex causes for PSSD . From serotonin to Hormones For example

Since SSRI's also downregulate 5-ht2a and 5-ht2c, as well as type 1 desensitization. The big issue is now all of the other type 1 subtypes, and their corresponding inhibition of dopamine,NMDA, glutamate, acetylcholine etc....also oxytocin decreases are a big one.
I also see cortisol and prolactin increases being issue, and possibly too much endorphin/opioid buildup.
For this reason, the etiology of low estrogen-induced sexual dysfunction and high serotonin is very similar, but not necessarily simultaneous.
Because both serotonin and estrogen are prominently opposite, estrogen being a type 1 down regulator and type 2 upregulator, but estrogen in the sense of that derived from free testosterone...which we all know plays a major role in sex drive and sexual responsiveness

But rarely do we talk about dopamine  down-regulation  that can often play a major role In PSSD.  There are many causes For dopamine down-regulation.

- some are SSRI'S induced
- some are Induced by an adverse reaction to SSRI's and Anti-psychotic
- Some are induced by Doing certain things like  street drugs like Psycho-stimulant - methamphetamine,methylphenidate, Weed and cocaine
- too much stress & Esp - Excessive Porn and masturbation can lead to over-stimulation of the dopamine receptors which  results in down-regulate them(In my case) etc etc

You will often find people who are suffering from PSSD also have issues like depression and especially Numb emotions, lack of Motivation... Feeling zombie from Inside - this condition is called Ahnedonia and is a cause of Dopamine down-regulation in which the dopamine receptors don't respond to Stimuli so naturally When the receptors don't respond people will often feel numb since dopamine plays the major role In the reward department ..

Go to any psychiatrist and complain about this they will prescribe you Wellbutrin 150 mg or 300mg . This is the most common treatment or a notion accepted for sexual side effects and esp PSSD from ssri's

But it doesn't work for most people suffering from PSSD. There are two reasons for this -

1) Wellbutrin Has most affinity for norepinephrine and has a weak affinity(33%) for dopamine transporter

2) If you suffer from ahnedonia - It will not work in cases where receptors are down-regulated. no matter how much neurons are left there to be used the receptors won't respond to stimuli !

Here Jason will explain in detail about Dopamine down-regulation and how to Up-regulate them effectively and long term

To Rewire dopamine there are many things that could be done

Getting hormones in control would be one

Good diet,Exercise,Intensity workout and resistance training would be one way to do that long term

http://www.reuniting.info/node/7200
www.mdpi.com/2076-3425/3/1/39/pdf

xx More will be Updated xx

Thanks admin, Will roger that ! I have been reading these a lot so would like to clear out -

Since we know exercise rewires dopamine there are a few more things -

1) Does meditation rebuild dopamine signalling ?

2) Does fasting do that ?

2) I have often read about a drug called "selegiline" However I have read in some places it down-regulates the dopamine receptors but on many places It says it increases the dopamine receptor ?
which one is it ?

3) how long after getting hormones in check and taking all the supplements and starting intense cardio can one expectto see the reversal of ahnedonia ?

forexworld12 wrote:Thanks admin, Will roger that ! I have been reading these a lot so would like to clear out -

Since we know exercise rewires dopamine there are a few more things -

1) Does meditation rebuild dopamine signalling ?

2) Does fasting do that ?

2) I have often read about a drug called "selegiline" However I have read in some places it down-regulates the dopamine receptors but on many places It says it increases the dopamine receptor ?
which one is it ?

3) how long after getting hormones in check and taking all the supplements and starting intense cardio can one expectto see the reversal of ahnedonia ?

Excercise helps to stimulate dopamine neuron growth, androgen activity , and also helps to increase histamine and nitric oxide levels, especially hard resistance exercise and cardio-endurance tasks!

It also eventually will-help re-map the 5-HT1A gene encoding and balance out the sympathetic nervous system, providing there isn't another deficit or hormone imbalance, a goal of everyone should be to reduce body fat as well, because this can cause issues in all departments....if one is carrying extra weight , particularly on their abdomen and chest.

Meditation helps indirectly due to helping the stress hormone balance.

I dont belive ssris downregulate dopamine, they do the opposite, they upregulate dopamine receptors in compensatory action....

you are correct that 80% of people with ppsd also have anhedonia....but heres the rub of it

I know people with complete emotional anesthesia, they cannot feel ANY meotion good or bad......but they dont have pssd, can reach orgasm etc etc

I know people with severe PSSD who have a normal emotional range

there is definitly a connection with the 5ht1a receptor...as many drugs that cause anhedonia or complete loss of emotion good or bad work on the 5ht1a potently but are not ssris.....

but what we dont know is why.....even recently in ketamine trials the area that was ativated and restored normal functioing with emotions (not perenantly) was different to what was expacted, and it was the dorsal anterior cingulate cortex

now I have every symtpom of low dopamine, I have akathisia, arkinsons like tremor the list goes on and on...but my emotions are in tact

I seems to me that 5ht2a inhibits dopamine release in the VTA hence my symptoms, i do not have pssd and I do not have anhedonia

but in my case its more easily explained,,,,5ht2a recetors rebound at 4-6 months off an ssri...the sudden upregulation (now at increased numbers due to kindling) inhibits dopamine in the VTA...this is a tardive condiiton, similar to tardive dyskinesia

3 years on with akathisia im developing tardive dyskinesia as the brain attempts to compensate the lack of dopaine by upregulating receptors

so we know with pssd that dopamine downregulation cannot be the case...the receptors would upregulate in the presence of too little dopamine......

there is some connection between downregulation of 5ht1a and pssd AND anhedonia...but we dont know what yet

it cannot be that with downregulated pre synaptic 5ht1a there is a flood of serotonin to the brain inhbiting dopaine as the other receptors would downregulate in response to this massive influx of serotonin....or maybe that does happen.....hmmmmm

Well actually, long-term SSRI use suppresses dopamine signaling. It also causes changes in CREB cycles and phosphorylation of multiple genes. The 5-HT1A autoreceptors get de-sensitized which results in excessive serotonin at the post-synaptic 1A receptors...this side of the 1A is BAD on multiple levels..if agonized in excess, the particular post-synaptic 1A creates an anxiogenic (anxiety filled) atmosphere and will also lower dopamine by negatively regulating nitric oxide levels.

yes dopamine signalling, but not downregulation...as I said a reduction in dopamine will result in an UPREGULATION of dopamine receptors.....which is why I have both PGAD and tardive dyskinesia as a result of having akathisia for so long

I guess the 5hta post syn recepotrs could well be the answer

can you go into how 5ht1a and nitric oxide are connected please?

you see (i thought I had posted this) a guy came on the ssri damage forums years ago..he had discontinued lexapro and been ok....he then took a NO suppliment that claimed to rasie NO by 950%#

he immediatly became emotionaless and had complete PSSD.....not just pssd but he was dead inside, a total zombie....

if NO somehow works through the 5ht1a autoreceptor this would make alot of sense, but i thought serotonin lowered NO.....but there has to be some connection to the 5ht1a receptor....

ive looked online and found a couple of studies that are not easy to interpret and I cant post links.....would you be able to look for me please? this could really be helpful for us

Iggy131313 wrote:http://www.medicine.osu.edu/neuroscience/documents/RandyPapers/2003/HB2003.pdf

That article is stating that nitric oxide deficient mice have increased aggression, this could be for a variety of reasons...

1.) Less vasodilation results in neural changes that may include adrenaline overload and / or disinhibition or via direct exchanges and molecular feedback.

2.) Lack of neural nitric oxide most likely leads to glutamate excess or deficiency, both of which can cause aggression, albeit by different mechanisms.



HOWEVER..the study I was referring to in relation to dopamine is how nitric oxide plays a role in depression, and that low levels will not only increase risk of depression but also cause dopamine to be unusable. The main way, is that deficient nitric oxide leads to INCREASED reuptake of dopamine which is characteristically opposite of what aderral and ritalin do, which is to inhibit reuptake...in other words , less nitric oxide = more dopamine breakdown and less dopamine overall...so ADHD sufferers often have low nitric oxide.

Read these studies,

http://www.ncbi.nlm.nih.gov/pubmed/21335097


ftp://194.225.54.67/USFUL%20INFORMATION8-12-89/EDUCATIONAL%20%20INFORMATION/General%20informations/NO/Nitric%20Oxide/NO-Nervous%20system/NO-Dopamin%20transport.pdf


NOW HERE'S THE ONE ABOUT 5-HT1A's inhibiting nitric oxide levels and such..

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1572268/


IN CONCLUSION...

• overactivation of serotonin 1A post-synaptic receptors LEADS to inhibition of nitric oxide which leads to INCREASED recycling of dopamine and less dopamine activity by a central mechanism, an effect that could be partially but not fully reversed by inhibiting dopamine reuptake.
  
• NMDA receptors are inhibited by serotonin which leads to not only less nitric oxide but an increased susceptibility to anxiety, psychosis and other dramatic effects.
  

hmmmm, well there must be a reason why the massive amount of NO caused that guy the same as many people with pssd have...

that study I posted is the first I have seen that links 5ht1a to emotion....its a breakthrough

if overactivation of 5ht1a leads to inhibition of NO...I guess its possible that overactivation of NO might cause the brain to downregulate 5ht11a as *it* controls NO release?

Iggy131313 wrote:hmmmm, well there must be a reason why the massive amount of NO caused that guy the same as many people with pssd have...

that study I posted is the first I have seen that links 5ht1a to emotion....its a breakthrough

if overactivation of 5ht1a leads to inhibition of NO...I guess its possible that overactivation of NO might cause the brain to downregulate 5ht11a as *it* controls NO release?

Having LOW N.O is not a good thing, and will damn your mood and libido!

interesting, thanks for all you hard work area! plz PLZ find us the cure!!

Bumping this for it's value.

Our main article updated!

Step-by-Step Guide How to Use Supplements to Reverse/Prevent Dopamine Downregulation



In/Tags: Step-by-Step Guide How to Use Supplements to Reverse/Prevent Dopamine Downregulation