Why does the brain develop a tolerance for dopamine?

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Why does the brain develop a tolerance for dopamine?

In: Biology

Is it a tolerance or more of a cellular fatigue with damage from use?

Do you mean tolerance as in needing drugs to produce it once addicted? That’s because the natural sources of dopamine in the body have greatly reduced production in response to the increase from this new source.

In short, your brain tries to build a resistance to everything it does not need. Basically, food, water, and air. And their are cases where the brain has attacked those too.

Imagine you’re a neuron, your job is to send emails (dopamine) to your colleagues (more neurons). You start your shift at Brain Inc. and you receive an email that says something good happened so you start to inform your colleagues through your own emails. You fellow neurons receive the message in their inbox (receptors) and send it on. To make sure that their inboxes don’t get cluttered there is a system in play that removes the emails after some time.

Now imagine that instead of something good happening someone used cocaine. Instead of you sending the email and it getting cleared after sometime, your colleagues keep seeing the email in their inbox. At first the would do their job very well all sending on the email to even more colleagues, but after sometime some of your colleagues would close their inbox performing a worse job. This continues until very few inboxes are left.

At this point you would say that there is a tolerance, because you either need to wait untill all the inboxes open up again but accept a worse performance in the meantime or increase the dose to make sure you completely flood the still open inboxes to keep the performance the same at the risk of closing even more inboxes.

I hope my explanation cleared up some of your questions and if I need to further clarify anything,I’d be happy to.

Because our body wants balance.

Our body strives toward what is called “homeostasis” where things are balanced out. Starting to feel too hot in the sun? Release some sweat to cool down. Didn’t drink that much water today? Your pee is gonna be yellow due to your kidneys concentrating your urine to retain as much water as possible.

This applies to everything including “brain chemicals” such as dopamine. Dopamine does X. More dopamine does even more of X. Over time time, there is still lots of dopamine, so body will make it so that there is less of X even though there is still lots of dopamine. Why? Our body wants balance. So that high level of dopamine is now the new standard, leading to tolerance.

Since this is an ELI5, keeping it simple, but there is a lot to dive into for tolerance and body homeostasis.

You don’t get tolerance from dopamine, if that would be the case our lives would be fucked up. DOpamine is involved in motricity, vision and motivated behavior and is secreted all the time with highs/lows depending on what you do.

The closest thing you get from dopamine tolerance is when heavily using cocaine you can affect the balance between dopamine receptors D1 and D2, but that’s because cocaine block our dopamine recapture system causing a massive surge of dopamine (300% of the baseline release if my memory is correct).

D2, which kind of acts like a brake on dopamine neurons, becomes downregulated in some brain regions and that participates in making you crave more and more drugs because the reward system never cools down and gets stuck on a loop of wanting more

To look at it from an evolutionary standpoint, it’s useful for your brain to adjust what it considers normal to match what’s around it. This means that the relative significance of an unusual event is amplified, because it stands out from the normal. Your brain doesn’t have an infinite range of response to events so shifting the response to the most sensitive region makes it easier to react to events.

A non-drug example of this is danger. Modern life contains very few life threatening dangers but it is useful to avoid being injured. As a result, your brain changes your pain tolerance to make you more likely to avoid small injuries that you might have shrugged off if you lived outdoors all the time.

So, your brain doesn’t develop resistance to it so much as it learns to ignore the constant shouting so it can focus on optimising you for survival in any environment. This has the unfortunate effect of making it near impossible to be constantly happy, no matter your life circumstances.

From an evolution point of view, humans require a lot of different resources, so spending all of your time only doing one thing, lowers your chance of survival.