GABA A upregulation after surgeries. And CFS and neurocognitive disorders

[Helen]

GABAA Receptor Theory of Perioperative Neurocognitive Disorders | Anesthesiology | ASA Publications

they suggest to use A-2 agonist here to reverese gaba a overexpression. interesting as I suggested a-1 antagonist in another thread. Since a-1 and a-2 go opposite of each other.


Worth to mention that some people recovered from PSSD using MDMA which is a-2 agonist. Role of α2A-adrenoceptors in the effects of MDMA on body temperature in the mouse | Request PDF

Cortisol supplements also downregulate Gaba A , which is why we had recoveries on licorice, lithium, etc.


This is mostly to low cortisol people slow oxidizers.


@Jaxx @barbaar @talkingant

 

[Helen]

Let not forget finasteride in some cases kills both gaba agonizing things allopregnenolone and 3 adiol, so it could also cause gaba a overexpression.

 

[Nina]

MDMA works on serotonin receptors no? So if it increases the serotonin levels, wouldn’t that mean the serotonin would go down after you stop using it thus cortisol also goes down?

End effect being even lower cortisol levels.

 

[Helen]

@barbaar Direct link between GABA activation and dopamine suppression

 

[Aflac94]

GABAA Receptor Theory of Perioperative Neurocognitive Disorders | Anesthesiology | ASA Publications

they suggest to use A-2 agonist here to reverese gaba a overexpression. interesting as I suggested a-1 antagonist in another thread. Since a-1 and a-2 go opposite of each other.


Worth to mention that some people recovered from PSSD using MDMA which is a-2 agonist. Role of α2A-adrenoceptors in the effects of MDMA on body temperature in the mouse | Request PDF

Cortisol supplements also downregulate Gaba A , which is why we had recoveries on licorice, lithium, etc.


This is mostly to low cortisol people slow oxidizers.


@Jaxx @barbaar @talkingant

Would taking cortisol vs running RU be opposites or just different ?

Like if you are suggesting cortisol cycle for slow oxidizers , should RU be avoided?

Cortisol would suppress vs ru would up regulate after the cycle , am I thinking about it right?

 

[Nina]

@barbaar Direct link between GABA activation and dopamine suppression

Does low/no dopamine also mean low adrenaline/norephedrine? As they are created from dopamine?

 

[barbaar]

@barbaar Direct link between GABA activation and dopamine suppression

Sounds like me, 0 reward system for anything. I'm confused though because on my tests dopamine was high.

 

[RebelWithACause]

@barbaar Direct link between GABA activation and dopamine suppression

Yes this is why phenibut and GHB cause dopamine rebound!

 

[Aflac94]

I would think Gaba supplements or benzodiazepines would down regulate gaba

Would think alcohol too , but that never helped me. I don’t feel any response to it

 

[Aflac94]

Shit is complex

“Consistent with a role of extrasynaptic GABAARs in the regulation of the HPA axis, a significant increase in GABAAR α5 subunit expression and a decrease in GABAAR δ subunit expression have been demonstrated in the PVN following stress”

“Neurosteroidogenesis has been demonstrated to be essential for steroid hormone-linked alterations in GABAAR subunit expression (Maguire and Mody, 2007). These alterations in GABAAR subunit expression following stress are likely mediated by neurosteroid-mediated effects on GABAAR phosphorylation (Brussaard and Koksma, 2003), which controls GABAAR expression [for review see Kittler and Moss (2003)]. These data demonstrate the complex actions of both steroid hormones and neurosteroids on GABAARs via direct modulation or by altering receptor expression.”

The reciprocal regulation of stress hormones and GABAA receptors

“The findings highlighted in this review demonstrate a reciprocal regulation of stress hormones and GABA receptors, in that GABAergic transmission plays a key role in the regulation of the HPA axis and the production of stress hormones and stress-derived neurosteroids can alter GABAAR subunit expression as well as directly modulate GABAergic transmission.”

 

[Aflac94]

Basically what I got from that was neurosteroids control the expression of different gaba receptor types.

The balance of different gaba receptor types is essential to HPA

Finasteride = screwed up neurosteroid balance = screwed up Gaba receptor subtypes = broken HPA axis

 

[Aflac94]

Neurosteroids can potentiate the tonic component of GABAergic inhibition via action on GABAAR δ subunit-containing receptors at low concentrations (Stell et al., 2003), can potentiate the phasic component of GABAergic inhibition at higher concentrations, and at very high concentrations have even been shown to directly gate the receptor [for review see Lambert et al. (2009)].

“inhibition can be "phasic" or "tonic". Phasic inhibition is a short-lasting inhibition typically generated by the activation of GABAA receptors following action potentials in a presynaptic interneuron. However, there are also more long-lasting forms of inhibition.... A second form is the "tonic" GABAA conductance activated by ambient GABA in the extracellular space (Farrant and Nusser, 2005). This form of inhibition is mediated by molecularly and functionally specialized GABAA receptors. These receptors contain alpha6 or delta subunits, which display a high affinity for GABA binding...”



Wish I knew what this meant , “gate the receptor” , prevent the channel form opening??

 

[Aflac94]

“..steroid hormones themselves can alter synaptic GABAergic transmission (Maggio and Segal, 2009). Corticosterone alters the frequency of spontaneous sIPSCs in the hippocampus via actions on MRs (Maggio and Segal, 2009) and increases the amplitude of sIPSCs via actions on GRs (Maggio and Segal, 2009).”

Looks like cortisol increases frequency of inhibitory Gaba current in hippocampus , if I interpret this correct ?

 

[Aflac94]

Neural inhibition - Scholarpedia

Damn

 

[talkingant]

They say in the paper that a2 agonists release BDNF. This has been a subject of interest recently on the PSSD forum, and might explain recoveries with psychedelics.

It also appears there is a link between GR activation and GABAA. For people like me with low cortisol, we could have hyper sensitive GR which leads to improper regulation of downstream systems like GABA. This may be why some people recovered with licorice root, which raised their cortisol and downregulated their oversensitive GR.

 

[Helen]

They say in the paper that a2 agonists release BDNF. This has been a subject of interest recently on the PSSD forum, and might explain recoveries with psychedelics.

It also appears there is a link between GR activation and GABAA. For people like me with low cortisol, we could have hyper sensitive GR which leads to improper regulation of downstream systems like GABA. This may be why some people recovered with licorice root, which raised their cortisol and downregulated their oversensitive GR.

yes we have talked about possible cortisol receptor upregulation. I suggested this theory https://www.hackstasis.com/threads/pssd-latest-thoughts.1358/


question is, is the problem coming from cortisol receptor. OR The problem is in gaba receptor

In any case cortisol supplement should work.

 

[Crashing]

can GABA receptors be implicated in my tinnitus?

 

[Blugrass]

What about phenibut?
I'm not entirely sure if this is related to your theory, but In 2017 I had a whole month of no shrinkage at all after taking medium doses of phenibut for a few days.

Then I took iodine and that fucked me up completely and shrinkage came back with a vengeance.

I would like to try phenibut again, the problem is that these days if I take just a little bit I feel like death for two days, so I can't go to higher dosages. Not sure why this is happening now. I wish I can find a way to overcome this side effect

 

[Blugrass]

Also chamomile has high affinity to GABA A and long half life (I heard 90 hours)
If I take just a few sips of chamomile tea, I feel very sleepy for days. It also has gives you withdrawals after you quit it. I never drank it in high amounts.

 

[Nighteyes]

Also chamomile has high affinity to GABA A and long half life (I heard 90 hours)
If I take just a few sips of chamomile tea, I feel very sleepy for days. It also has gives you withdrawals after you quit it. I never drank it in high amounts.

But shouldnt This help downregulate the receptors and thus help slow oxididers with upregulated GABA ? Maybe 1 week on 1 week off?