This is a guest article written by Mogelfur, Wolf Den Wolf Pup (WDWP) # 4936. He covers his personal synopsis of the content by Prof. Huberman, which he has consumed so far, available through his podcasts and associated videos on YouTube. A link will be left in the references section for Andrew Huberman’s content library.
Disclaimer: This article neither attempts to be scientifically correct, nor should be regarded as medical, or behavioral advice. The following content attempts to break down the published and presented concepts of dopamine regulation and its (projected) impact on human behavior, based solely on Mogelfur’s personal understanding. Consume with care and DYOR!
With that, let’s begin.
Since I’m a biologist with a knack for chemistry, here is the chemical structure of dopamine and a few associated molecules:
Scheme 1: A scheme of the synthesis of epinephrine over dopamine out of L-tyrosine as a substrate, as presented in text book knowledge. Reaction names and intermediate steps are taken out to improve readability.
So, dopamine is actually formed of an amino acid, called tyrosine (or L-tyrosine to be precise, but in our biological systems the D- variant is not regarded to be of importance if my memory does not fail me) and is tightly associated with a hormone telling you to go in a state of high alert, epinephrine. Which is another name of adrenaline.
Why is this of importance and do I have to torture you, dear reader, with chemistry?
Well, dopamine is a neurotransmitter and the point here to make is, metabolism, in general, is in a permanent steady state. If you deplete, or externally spike, any of the ingredients, you will have an influence on the regulation. Reaction kinetics are dependent on the concentration of both the substrate, and the product. If you have a lot of epinephrine, it will be much harder to get more of it out of the pool of dopamine, if you do not increase the amount of fabricators to increase the production rate again. Likewise, having no L-tyrosine will make it hard to get either dopamine, or epinephrine. Plus, supplementing exogenous chemicals will force your metabolism to adapt to create homeostasis again – any spike that you may, or may not, want to introduce into a biological system, can and will have impacts/backlash on the system as a whole. Let’s say, if you’re constantly in fighting mode and maxed out of epinephrine, you might develop a lack of dopamine in the long run due to exhaustion.
Feeling safe and safe-regulation are equally as important as other behavioral modifications you might be able to do, but the topic of safety and feeling safe is a completely different topic on its own. I highly recommend to give the booklet “The Polyvagal theory“ by Stephen W. Porges a good read; if you never thought about safety and how feeling safe forces your body into specific reaction modes, it blows your mind away.
Again, I got carried away, but this whole topic is rather complex, so please drop me a message (The Guardian Academy discord name “Mogelfur”) in case of need for further clarification. At least I can for sure, only profit from that :).
Dopamine- A Neurotransmitter
As previously stated, dopamine is a neurotransmitter. What is a neurotransmitter? Well, it helps in delivering a message between two cells, located in your brain. However, biological systems are not that simply built, so basically you have a cell that sends a message and one that is prepared/preparing itself to receive a message. And both are basically waiting for their moment to hit the button (deliver the message or forward it), albeit with different kinetics. This is further illustrated in the following scheme:
Scheme 2: Scheme of a receiver and a transmitter cell in the pre-synaptic furrow, with receptors and neurotransmitter filled vesicles. Vesicles are stored for an in-demand release into the pre-synaptic furrow, where receptors can report dopamine binding through the cell membrane (shown as blue borders). Repeated triggering of release results in vesicle depletion, which returns a feeling of low driven-ness. Depending on the time between the events, a repeated trigger of this mechanism results in an incrementally decreasing amount of receptors reporting dopamine binding, which in turn results in a decrease of transmitted signal intensity throughout the cell (since a lower fraction of receptors are reporting than before). This‚ habituation results in a sense of dullness, in respect to the neuronal pathway activated. While an increase of the very same dopamine receptors seems not to be associated with a decrease of dopamine response (you can actually increase the amount of receptors by drinking caffeine containing beverages like coffee and tea leafs of Camillea sinensis), other dopamine-receptor-like proteins are expressed to mediate habituation. The molecular mechanism is, to the best of my knowledge, not well understood.
We have a pre-synaptic furrow, which acts as a space between a messenger and a receiver, much like a phone cable back in the days when phone cables were still a thing. You can think of vesicles – small drops which i would like to compare with bubble-tea-bubbles – carrying dopamine (or other neurotransmitters) in them. When the messenger is triggered, it releases the dopamine inside the vesicles into the furrow, which in turn leads to dopamine binding at the receptor. The bubbles now need to be replenished – once the pool is empty, no more transmitting. Repeatedly hitting the same button and activating the same pathway, will lead to something called habituation – you are getting used to a certain stimulus.
Why Is This Important?
Well, dopamine has been correlated with the seek-and-reward behavior of mammals. We are mammals. And we are displaying seek-and-reward behavior – we want the apple if we’re hungry, we want to drink when we are thirsty. This might seem to be self-explanatory, but anyone who has ever tried to assemble some code to tell a machine what to do, knows that sometimes the easiest things are actually quite difficult to put into an algorithm which works flawlessly. You could be hungry all that you want – but without actually feeling the painful DESIRE to change that state, you won’t go anywhere – and thats where dopamine comes into place. Interestingly enough, getting a reward again leads to an increase of dopamine and feeling rewarded– but now here’s the problem: if you studied scheme 2, you will see that getting dopaminergic triggers actually depletes dopamine and reduces the ability of the pathway to trigger the very same pathway again. We can try to simplify this by the following curve:
We can see here, that a reward is associated with a lowering of dopamine response (baseline of dopamine). Thus, rewards lead to a decrease of seek-and-reward associated behaviour. You might now rightfully wonder, if life actually doesn’t want us to be happy – well, given that in former times – speaking from an evolutionary perspective – a readily available entertainment industry was NOT waiting to give us any hedonistic pleasure that we might enjoy, was probably the thing to actually circumvent never wanting to stand up and do something again. Funnily enough, the actual reward system actually has another, dopamine per-se independent component to it, which allows you to still be able to enjoy stuff – just not actually wanting to do something (for) it. Personally, I experience this state when I’m sitting in front of my computer and starring at my filled Steam-Library for three hours, without actually playing any game. Procreating is actually a strong dopaminergic stimulus. Bonobo-primates, for example, have been observed to let males mate the females, only for the females to then start distributing resources when exploring a new area with new trees etc., among the pack. It seems plausible, that the observed behaviour reduces the ‘desire’ of males to invest themselves into splitting the new resources, however I have no scientific evidence for this claim.
The Good Message
If you leave the pathway alone for a sufficient time, things will go back to normal. Another interesting thing: Suffering will actually increase the perceived reward of a certain behavior, or endeavor – which probably makes eating a bliss after a period of prolonged fasting. But, and this is what was until today a mystery for me: Prof. Huberman recommended to not stack too many dopaminergic effectors on top of each other in order to actually still want to enjoy a special activity. This would lead to an intense spiking of dopamine response, which results in an equally – if not more drastic – crash. However, I was wondering what actually changes the perception of the activity in a more broader concept – and here, it struck me that dopamine is a
universal currency: there is only dopamine mediating this activity and nothing opening a second loop, telling you that the thing that you wanted to make enjoyable, or even endurable (like doing very dull chores) is actually over and also deprives you off of the reward you would receive with it. This actually, if you follow the above schemes, leads to an ever-growing aversion against the activity, or makes the actually enjoyable activity dull without extra spice in the soup. And this can swiftly grow into addictive spirals if combined with drugs, or other strong stimulants (in regard to dopamine response), but this is content for another story.
This synopsis is radically simplified and should not be regarded as scientifically complete, but I think there are rather interesting implications which one can derive from this depiction of dopamine-pathways. Constantly trying to entertain oneself seems to be a bad idea (if one wants to be a driven individual), but periodically re-occurring time frames of low agitation seem to be necessary to keep homeostasis and the system in a sustainable state over a longer period of time. To put it more simply, it seems necessary to include (a) routine behavior(s), much like washing hands after using the toilet, to maintain a healthy neuro-transmission system.
Hope this was interesting and best regards,
Mogelfur, Wolf Pup # 4936
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- Andrew Huberman- https://hubermanlab.com/