what receptors control the amygdala?

[trainman04]

since the amygdala is what controls fear and everything related . Would decreasing the activity reduce anxiety and fear?
My question is what receptors control the amygdala activity?
I know Alpha-7 nicotinic receptor controls it but is that it or is there more receptors and stuff involved?

Because if thats it . I can just take Memantine or wellbutrin which are antagonist on Alpha-7 nicotinic receptor thus it should reduce amygdala activity right.

Lemme know if there are more receptors etc that you need to target that are connected to the amygdala.

 

[Cotcha Yankinov]

The amygdala is certainly more complex than just "increase in amygdala activity = fear", and it controls so much more than just fear/anxiety related behavior. But there are different parts of the amygdala that do different things, and even different types of release of the same neurotransmitter can signal very different things.

As an example, in some cases, a larger amygdala can be associated with better emotional regulation, while a smaller amygdala can be associated with an increased risk for bipolar disorder.

But a lot of anxiety/fear/PTSD is glutamate neuroplasticity related, although the amygdala (especially basolateral amygdala) can be largely e.g. GABAergic. Though most GABA neurons co-release glutamate.

One thing to consider is that a multitude of brain regions/structures provide input to the amygdala and help regulate it and these various other brain structures will have an incredible multitude of receptors. So I wouldn't say that there is any one "amygdala receptor".

 

[trainman04]

The amygdala is certainly more complex than just "increase in amygdala activity = fear", and it controls so much more than just fear/anxiety related behavior. But there are different parts of the amygdala that do different things, and even different types of release of the same neurotransmitter can signal very different things.

As an example, in some cases, a larger amygdala can be associated with better emotional regulation, while a smaller amygdala can be associated with an increased risk for bipolar disorder.

But a lot of anxiety/fear/PTSD is glutamate neuroplasticity related, although the amygdala (especially basolateral amygdala) can be largely e.g. GABAergic. Though most GABA neurons co-release glutamate.

One thing to consider is that a multitude of brain regions/structures provide input to the amygdala and help regulate it and these various other brain structures will have an incredible multitude of receptors. So I wouldn't say that there is any one "amygdala receptor".

what receptor would i need to target to decrease amygdala activity?

 

[sekio]

One thing to consider is that a multitude of brain regions/structures provide input to the amygdala and help regulate it and these various other brain structures will have an incredible multitude of receptors. So I wouldn't say that there is any one "amygdala receptor".

--^ That.

 

[freqsoft]

since the amygdala is what controls fear and everything related . Would decreasing the activity reduce anxiety and fear?
My question is what receptors control the amygdala activity?
I know Alpha-7 nicotinic receptor controls it but is that it or is there more receptors and stuff involved?

Because if thats it . I can just take Memantine or wellbutrin which are antagonist on Alpha-7 nicotinic receptor thus it should reduce amygdala activity right.

Lemme know if there are more receptors etc that you need to target that are connected to the amygdala.

Think of the Amygdala like an ORGAN of the brain.

It generates and regulates production of catecholamines (epinephrine, norepinephrine, and dopamine) which then go on to bond to receptors, affecting your mood and behavior. You're on the right track with researching alpha-7's (α7-Containing nicotinic acetylcholine receptors), as they are located on the interneurons of the basolateral amygdala, which controls and regulates how hyphy your neuro-network is going to be for the moment, but also consider Notch receptors, trkB and trkC receptors, and androgen receptors; and any ligand that stimulates the dorsolateral prefrontal cortex will decrease activity in the amygdala.

Hope that helps.

Great topic for discussion. I'm curious as to your motivations for asking.

what receptor would i need to target to decrease amygdala activity?

Glutamatergic N-methyl-D-aspartate receptors when activated heavily suppress the amygdala. NMDAR's is your answer.

So I wouldn't say that there is any one "amygdala receptor".

--^ That.

Not necessarily true. Androgen receptors are heavily associated with the amygdala. If any one receptor has the MOST power of it, it's this. Testosterone and the limbic system are like peanut butter and jelly.

Awesome thread. The entire amygdaloid complex is truly fascinating.

Let's keep this going.

 

[trainman04]

Think of the Amygdala like an ORGAN of the brain.

It generates and regulates production of catecholamines (epinephrine, norepinephrine, and dopamine) which then go on to bond to receptors, affecting your mood and behavior. You're on the right track with researching alpha-7's (α7-Containing nicotinic acetylcholine receptors), as they are located on the interneurons of the basolateral amygdala, which controls and regulates how hyphy your neuro-network is going to be for the moment, but also consider Notch receptors, trkB and trkC receptors, and androgen receptors; and any ligand that stimulates the dorsolateral prefrontal cortex will decrease activity in the amygdala.

Hope that helps.

Great topic for discussion. I'm curious as to your motivations for asking.


Glutamatergic N-methyl-D-aspartate receptors when activated heavily suppress the amygdala. NMDAR's is your answer.



Not necessarily true. Androgen receptors are heavily associated with the amygdala. If any one receptor has the MOST power of it, it's this. Testosterone and the limbic system are like peanut butter and jelly.

Awesome thread. The entire amygdaloid complex is truly fascinating.

Let's keep this going.

**It generates and regulates production of catecholamines (epinephrine, norepinephrine, and dopamine)**

What about serotonin to the above statement?


Just the alpha-7 or the other alpha receptors too has effect on the amygdala?

someone told me the nicotinic Alpha-7-receptor controls much the activity in and out of the amygdala, by antagonising it, activity is drastically reduced. is that true?

**Glutamatergic N-methyl-D-aspartate receptors when activated heavily suppress the amygdala. NMDAR's is your answer.**

So increasing NMDA is the best way to reduce amygdala activity, how does that work?
Because I have tried memantine and it worked great for my anxiety- its an NMDA antagonist.

Is taking N-Methyl-D-Aspartic Acid best way to increase NMDA? like this product ( https://www.bodybuilding.com/store/iforce/intimidate-srt.html )

no idea what the Notch receptors, trkB and trkC receptors, and androgen receptors are or any ligand that stimulates the dorsolateral prefrontal cortex . do you care to describe a little bit of each ? you dont have to.

also what About kainate and AMPA role in the amygdala ?

 

[Cotcha Yankinov]

Not necessarily true. Androgen receptors are heavily associated with the amygdala. If any one receptor has the MOST power of it, it's this. Testosterone and the limbic system are like peanut butter and jelly.

While intra-amygdala injection of androgens do have effects on fear behavior, I do also recall androgens playing a big morphological/developmental role in the amygdala. If there is a study that compares side by side various intra-amygdala injections (not an androgen receptor knockout study that will affect morphology) I'd be curious to see it

I imagine Beta-2 adrenoreceptor antagonists would prove potent anti fear behavior agents in such an assay

 

[browri]

I imagine Beta-2 adrenoreceptor antagonists would prove potent anti fear behavior agents in such an assay

I noticed a pretty profound inhibitory effect on adrenaline from brexpiprazole through its alpha-adrenorecepter antagonism. It's actually one of my favorite qualities of its pharmacological profile because of how positive of an effect that it has had on my anxiety.

 

[Limpet_Chicken]

Nobody should be taking NMDAr AGONISTs. At least, not the main orthosteric site, the likes of ibotenic acid from fly agaric before its cured is an NMDA agonist, and its a potent excitotoxin, used in lesioning experiments to destroy pathways in animal brains and other sick, fucked up shit along those lines.

 

[trainman04]

what is the AMPA function in mood/anxiety?

 

[Cotcha Yankinov]

AMPAr contribute to a process called Long Term Potentiation that governs learning/neuroplasticity, and the brain largely develops anxiety through associative learning (e.g. I get shocked when the red light comes on, therefore I learn to fear the red light).

 

[trainman04]

AMPAr contribute to a process called Long Term Potentiation that governs learning/neuroplasticity, and the brain largely develops anxiety through associative learning (e.g. I get shocked when the red light comes on, therefore I learn to fear the red light).

so you wanna block AMP?

 

[sekio]

Blockade of AMPAr is probably not wise, as AMPA positive allosteric modulators are all nootropics like piracetam. Negative allosteric modulators are things like barbiturates and ethanol... so blockade of AMPAr will likely result in decreased cognitive performance.

 

[trainman04]

what about the kainate receptors? is it important in amygdala

 

[Limpet_Chicken]

IIRC KA receptors are less well understood than either NMDARs or AMPARs, but seem to be involved in setting how likely a neuron will fire in response to stimulation after previous stimulations and action potential discharges. Modulating excitability in response to previous AMPA/NMDAr activation.

They may also be involved in hyperalgesia, given that certain fungi of the genus Clitocybe, such as C.acromelalga and C.amnoelens contain acromelic acids, which are kainatergic excitotoxins, and the results of poisoning with either of these, results in a long-lasting and severe hyperalgesia and severe burning, tingling pains. tbat can last for a long, long time (years potentially), I forget if its hot, or very cold water that suffers immerse the affected extremities in to bring temporary relief from, but one or the other apparently does. And it is reputed to be exceedingly painful neuralgia and erythromelalgia that results from poisoning by acromelic acids.

AFAIK the acromelic acids are selective (or if not totally so, then in terms of pharmacological relevance, KA agonism and resulting excitotoxicity is the main effect of these mycotoxins). KAr is expressed heavily in the spinal cord, and rather than directly passing fast excitatory neurotransmission as do NMDARs and AMPARs, kainate receptors seem to have a more subtle role, in that they appear to modulate the likelihood that a given neuron will fire in response to excitatory stimulation.

Definitely not fungi I'd want to be poisoned by, especially considering the excruciating pain that results, and how damnably long-lasting it is. AFAIK KARs are heavily expressed within the dorsal root ganglion area of the horn of the spinal cord.

 

[trainman04]

So the previous guy said increasing NMDA is the best way to reduce amygdala activity is that true how are the two connected?

also what effects do AMPA agonists have on you? I imagine they would increase anxiety if the statement is correct that AMPA is involved in fear learning?
Anyone know of any AMPA agonists and antagonists???

 

[Cotcha Yankinov]

what about the kainate receptors? is it important in amygdala

These targets really aren't therapeutic options at the moment, I mean there was a group investigating AMPA antagonists for PTSD but they were just in pilot studies and such so that's a long way off from these things being available to humans.

But going back to what Sekio was saying, just because something like Perampanel helps with someone's anxiety doesn't mean that it is overall worth it because these drugs have so many other effects. Glutamate receptors are basically the fundamental receptor of the brain, more so than serotonin/dopamine et cetera, so blocking them is not without a wide range of consequences.

That is opposed to e.g. beta blockers, which can help some people enormously with some facets of anxiety/PTSD, although they are not necessarily cures (anxiety/PTSD can be things that need to be genuinely treated with CBT/meditation and such, rather than covering up the symptoms with drugs before other options have been tried)

 

[Cotcha Yankinov]

also what effects do AMPA agonists have on you? I imagine they would increase anxiety if the statement is correct that AMPA is involved in fear learning?

Drugs that increase the activity of AMPA receptors (called Positive Allosteric Modulators or PAMs) can increase anxiety, and I have noticed in a few people that they can strengthen the inner monologue/internal chatter that for many is problematic and contributing to their issues.

 

[trainman04]

Are the cannabinoid receptors involved with NMDA? I found a SNP I have :

**rs1049353 linked to the gene CNR1. Your genotype is TT, which is observed in 3% of all individuals reported. One study mentions that each T causes intestinal inflammation, a higher stress response, anxiety, a higher risk for depression (dependent on low BDNF) and more severe IBD (although later onset of it) (R).
Another study mentions that there's a 2.46X increased odds of major depression for those carrying the T allele
With this variation, the receptors also don't become significantly less sensitive when activated
The T allele may cause lower CB1 receptor numbers and less CB1 activation. = less NMDA activity ?
**
I read old posts someone said cannabinoid receptors interact with glutamate channeling .
Could this be causing my Overactive amygdala? Since NMDA surpresses the amygdala? and with low/bad NMDA activity = high amygdala?
And my GABA is low doesent NMDA increase GABA?
My neurosteroids are Also low doesent NMDA increase that?

can low NMDA activity lead to high serotonin in the amygdala? Is it possible I have a dysfunctional NMDA system due to the low activity Endocannabinoida systemet gene mutation I have?

 

[Limpet_Chicken]

As opposed to positive allosteric modulators such as AMPAkines, actual AMPA receptor direct agonists are neurotoxins, causing seizures, potentially fatal, and if they don't kill you, can turn you into a vegetable. Permanently. Also there are low-impact (safer) and high-impact AMPAkines, that differ in such things as the way they gate the channel in terms of ion flux, as well as causing, or not, BDNF release. High-impact types elicit BDNF release whilst low-impact ones do not, apparently.

In the case of high-impact types these elicit a far more robust response, and whilst can be nootropic in LOW doses, in high doses they can cause seizures and excitotoxicity. So one must know what one is doing with a specific drug to be able to dose safely.

Also there are flip and flop isoforms of AMPA receptors, although selectivity isn't common for one of these subtypes. IIRC its only PEPAP (or is it PEPA), I always forget, I mean the AMPAkine though not the opioid, is selective in this way, and is one of the very few known ones which are. Its one of the biarylpropylsulfonamide types, IIRC.