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what receptors control the amygdala?

Is it true that Glutamatergic N-methyl-D-aspartate receptors when activated heavily suppress the amygdala? how?
 
I think NMDAr activation in the PFC can suppress amygdala mediated fear responses, as well as enhance fear extinction.
 
Cotcha Yankinov said:
I think NMDAr activation in the PFC can suppress amygdala mediated fear responses, as well as enhance fear extinction.
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so how do you activate that? just take daspartic acid?

is Increased number of 5-HT2C and 5ht2a receptors in the frontal cortex a big issue could that increase serotonin activity somehow in the amygdala cause to to be overactive? A site called selfhacked says the 5ht2a and 5ht2c are the Root Cause of Anxiety. Also 5ht1a.
 
Anything that activates NMDAr directly is bad because that can lead to excitotoxicity and disruption of the normal function of NMDAr. More NMDAr activation isn't necessarily better, it has to be meaningful NMDAr activation, and a molecule that just spreads throughout the brain activating NMDAr left and right isn't going to lead to any meaningful increase in function.

I've grown to rather dislike sites like Selfhacked, they oversimplify complex things and can also contain numerous inaccuracies. They pander to particular populations for profit purposes.

Don't bother with sites like that, and watch out for obsessing in general. Chasing genuine understanding of neuroscience/pharmacology (from a textbook) isn't necessarily a bad thing if it gets your mind in motion but try not to obsess.
 

click for bigger version of the poster

Just according to this chart, the amyglada has metabotropic glutamate receptors (mGluR1-5), AMPA receptors (GluR1-3), NMDA receptors, both GABAA (several different subtypes) and GABAB receptors, CB1 cannabinoid receptor, glycine receptors, and also dopamine receptors of varying types. But wait, there's more! There's also expression of leptin receptors, corticotrophin-releasing factor receptors, different types of K+ channels, glucagon-like peptide receptor, tropomyosin receptor kinase B (TRKB, AKA brain derived neurotrophic factor/BDNF receptor), somatostatin receptor 2, transient receptor potential vanillioid 1 (TRPV1, aka capsacin receptor), vasoactive intestinal peptide receptor 2, and very likely some more undiscovered/unknown receptors or maybe even ones that were left off that chart for simplicity.

Keep in mind that not all cells of the amyglada are identical; any given cell will only have a subset of these many receptors, not all of them at once.

[pulls out soap box and stands on it]
I should take a moment to mention I also feel that it is necessary for anyone wishing to apply their knowledge effectively to approach the study of neurochemistry from a holistic perspective - all of these receptors and their complementary neurotransmitters are merely individual cogs in a much larger machine, that is to say, focusing on the activity (or dysfunction) of any one subsystem in vacuo ignores the many compensatory and regulatory loops inherent to the human brain and is going to leave you missing the forest for the trees, so to speak. For example: autoreceptors allowing for "feed-back" control of neural activity; receptor down/upregulation over the long term compensating for e.g. chronically high adrenaline or other hormones, to a limited extent; or even allosteric modulation where compounds don't necessarily activate, nor block, the neuron but instead alter either the sensitivity to stimulation, the intensity of neurotransmitter release when fired, or how rapidly the neuron can fire. It is exceedingly rare for there to ever be as general a relation as "more compound X = less compound Y".
[steps off soap box and puts it away in a nearby black hole... *WHUMP*]

As for metabotropic glutamate receptors themselves, there have been several drugs developed that bid to mGluR5 and either block (antagonists e.g. basimglurant) or decrease the activity (negative allosteric modulators e.g. fenobam) for, among other things, treatment-resistant depression, anxiety of various sorts, Parkinson's-induced movement disorders, smoking cessation, opioid cessation, obsessive-compulsive disorder, neuroprotective agents, autism, Fragile X etc. - not all of which are successful. Apparently side effects especially at higher doses include amnesia and psychotic behavior, and none are approved as drugs yet.

There have also been research into the usage of mGluR2/3 agonists as anxiolytics and antipsychotics as well (e.g. eglumegad, pomaglumetad), these seem to have a more tolerable side effect profile, but again none of them have been granted FDA approval.
 
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Well FDA approval is always a damn long process, save perhaps in times of absolute crisis (such as say, ZMAPP being used without full trials in healthy patients, given the recipient of the partially untested drug was somewhere in the region of 90% fucked, given it was ebola zaire being treated)

And treatment for autism? don't tell me your a curebie....yeech. If anything we need to be looking for therapies to INCREASE the incidence. Assortative mating seems to happen quite commonly. We tend to go for our own kind. But just increasing the chances by selective breeding isn't 100% reliable. Autie/aspie couples can still pop out NT kids unfortunately. Whats needed is the development of something equivalent to the morning after pill. Take it after the couple get it on whilst intending to get pregnant and guarantee superior offspring.

The curebie lot can get buggered :p
 
the guy that Said NMDA can surpress the amygdala really got me intrested in trying NMDA.. if my problem is overactive amygdala this should be my cure right
 
.. Amino acids kinda like NMDA don't really pass through the blood brain barrier, but you wouldn't want to take NMDA anyways because it functions as an excitotoxin, exciting brain cells to the point where they die, and can cause seizures et cetera.
 
you act like im gonna die . nmda in excess is dangerous. But in normal doses it can help allivate my anxiety.. whats your problem? you always manage to find anything negative but dont look at the positives .
NMDA agonist can increases GABA
increase neurosteroids (pregnenolone etc)
decrease amygdala activity
it doesent readily pass trough the bbb but it can .
 
trainman04 said:
you act like im gonna die . nmda in excess is dangerous. But in normal doses it can help allivate my anxiety.. whats your problem? you always manage to find anything negative but dont look at the positives .
NMDA agonist can increases GABA
increase neurosteroids (pregnenolone etc)
decrease amygdala activity
it doesent readily pass trough the bbb but it can .
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Show us clinical evidence that taking NMDA orally is a safe and effective treatment for anxiety

NMDA is used in studies to learn more about excitotoxicity of brain cells. It is dangerous, and impractical anyways.
 
if d aspartic acid was dangerous bodybuilders and regular gym goers wouldnt be taking it. it didnt become popular because it was toxic.
 
trainman04 said:
if d aspartic acid was dangerous bodybuilders and regular gym goers wouldnt be taking it. it didnt become popular because it was toxic.
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They don't take D-AA to exert effects on the brain, they take it for effects on NMDA receptors on the testes. Taking D-AA/NMDA with intent for it to affect the CNS to help with anxiety is a completely different matter.

Once again, luckily there are blood brain barrier issues, but if there weren't BBB issues then taking an NMDA agonist would be a horrible idea.

You're better off spending your time practicing mindfulness meditation and exercising rather than grasping at these straws, and do keep in mind that if you had a favorable response to Zyprexa/Olanzapine that you could keep exploring that. Keep in mind that is an atypical antipsychotic, and many people with psychotic type issues can benefit from such drugs. I am not a medical professional et cetera, but in my opinion, you fit a phenotype of a person that may have some psychotic type issues.

CY
 
Cotcha Yankinov said:
They don't take D-AA to exert effects on the brain, they take it for effects on NMDA receptors on the testes. Taking D-AA/NMDA with intent for it to affect the CNS to help with anxiety is a completely different matter.

Once again, luckily there are blood brain barrier issues, but if there weren't BBB issues then taking an NMDA agonist would be a horrible idea.

You're better off spending your time practicing mindfulness meditation and exercising rather than grasping at these straws, and do keep in mind that if you had a favorable response to Zyprexa/Olanzapine that you could keep exploring that. Keep in mind that is an atypical antipsychotic, and many people with psychotic type issues can benefit from such drugs. I am not a medical professional et cetera, but in my opinion, you fit a phenotype of a person that may have some psychotic type issues.

CY
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so? doesent matter what intend they take it for its still the same the dosages are the same.
30mg NMDA is = 3000mg d aspartic acid . people even take more than 3g d aspartic acid and are fine.

how much do u think crosses the BBB?
 
N-methyl-D-asparate, just like aspartic acid itself, are both charged at physiological pH and as such won't diffuse across the BBB. As a rule only non-charged substances can diffuse through the fatty membranes of the BBB. Aspartic acid, being a protienogenic amino acid, has a specific amino acid transporter that moves it into the brain though, but I don't know if NMDA has affinity for that same transporter. NMDA is motly used in in vitro models and not in live animals.

However, nobody taking aspartic acid or any other amino acid needs to worry about NMDA agonist activity, at any dose. Taking aspartic acid is not going to produce a psychoactive effect because it is not converted to NMDA. NMDA is actually totally synthetic and is not found in man or other living things.[ref] There are no enzymes that cause the synthesis of NMDA in man either.

wiki said:
NMDA is a water-soluble synthetic substance that is not normally found in biological tissue. It was first synthesized in the 1960s.
Click to expand...

Also, generally speaking, *no* amino acids are excitotoxic when taken orally, as the transporters begin to saturate and switch to zero-order kinetics (absorbing a fixed amount per time unit) at high loadings of amino acids (this is what limits gabapentin's bioavailibility), meaning the % absorption goes down with increasing dose.

---

limpy said:
And treatment for autism? don't tell me your a curebie....yeech
Click to expand...

Nope, just listing what's been attempted by others.
 
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what? so I ordered regular d aspartic acid.. will that not work to activate NMDA ?
from examine

In bacteria, D-Aspartic Acid can get methylated via the enzyme D-Aspartic acid methyl-transferase to become the excitotoxin NMDA (N-methyl-D-Aspartate), and uses S-Adenosyl Methionine (SAMe) as the primary source of the methyl group;[21] while NMDA was the first selective agonist for the NMDA receptor (donating its name), it is not a predominent transmitter endogenously formed in humans.[3]NMDA and D-Aspartate are both metabolized by the enzyme D-amino acid oxidase.[22]
 
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Sorry, sekio, should have specified, that curebie bit was meant to be tongue in cheek.

If you DID suceed in obtaining an orally active NMDA orthosteric agonist, you would very much regret it, if you survived the consequences and weren't left a vegetable.

As for aminoacid neurotoxins, are we limiting this to only proteinogenic aminoacids? because I can think of things like phenylalaline analogs for example that act as glutamate receptor antagonists.

Trainman, to give you an idea of what these excitatory agents DO to their victims..ibotenic acid is an NMDA agonist, and (via microinjection into specific nerve pathways) is used both to lesion (I.e permanently destroy) target areas of the brain.

(one natural source is the fly agaric mushroom, of ibotenic acid, but thankfully its not the most stable of substances and decarboxylates when the mushroom is prepared, as it must be. People eat them raw, look on erowid and compare-raw=poisoning and cooked to decarboxylate the ibotenic acid to muscimol and there is the potential for a plant ally.

Or heres another couple of excitoxins for you, and what happens to people that get fucked by them. Amnesic/amnestic shellfish poisoning, a phenomenon not entirely different from the infamous 'red tide' (although the paralytic saxitoxin is the culprit for red tide, both are due to algal blooms). Domoic acid is the culprit for the amnesic shellfish poisoning, primary symptoms are seizures and memory loss, learning disability and potentially, if you are lucky, death. Recovery is slow or absent. In other words, you are fucked and going to end up a basket case for the rest of your life.

Acromelic acid, IIRC works via kainate receptors, and its found in a pair of Clitocybe mushroom species, C.amnoelens and C.acromelalga, and cause a peculiar and protracted swelling and neupathic pain in hands and feet, primarily along with hypersensitive reactions to cold.
 
D-aspartic acid is present in all humans already - if you ingest proteins or amino-acid-rich foods then your body will produce aspartic acid from hydrolytic decomposition of those proteins. In fact your body *needs* aspartic acid to fucntion, it's one of the amino acids that make up all the protiens in your body!

If you read your quote it says clearly: while NMDA was the first selective agonist for the NMDA receptor (donating its name), it is not a predominent transmitter endogenously formed in humans

Also, D-aspartic acid, like any other amino acid, is too polar to effectively diffuse across BBB and will not produce psychoactive effects... none of the amino acids do, really.
 
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