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AxelBoldt t1_j27pcez wrote

Reply to comment by 86BillionFireflies in In Parkinson disease, why doesn't the adrenal gland fill the dopamine deficiency? by Actual-Pumpkin1567

But given that, how come we treat Parkinson's by flooding the brain with dopamine? We wouldn't shovel valves into an apartment to repair a broken toilet valve.

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86BillionFireflies t1_j28hxch wrote

>how come we treat Parkinson's by flooding the brain with dopamine

That's the neat thing! You don't.

You flood the brain with stuff to make dopamine, which lets the surviving SNc neurons release more dopamine, essentially amplifying the signals of the ones that are left. If they all died, L-DOPA treatment wouldn't work. Again, the really important thing is the neurons, what inputs they get, how they process those inputs, and where they send their outputs, not which chemical they are releasing. In fact, most work on realistically simulating the activity of networks of neurons doesn't even bother to simulate neurotransmitters in any way, except to say "when this neuron fires, that one gets excited by +2millivolts after a delay of 2ms" or something to that effect.

So in the valve analogy, it's like we're increasing the water pressure so that the semi-busted toilet valve can still sort of function.

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AxelBoldt t1_j294iox wrote

Thank you for that. Do the dopamine-releasing neurons take up L-dopa, turn it into dopamine, and then release it at the synapse?

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86BillionFireflies t1_j29xtcv wrote

That's exactly right! In the synthesis of dopamine, converting tyrosine to L-DOPA is the slowest step, so having extra L-DOPA available significantly increases dopamine production.

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AxelBoldt t1_j2ack46 wrote

And we're not concerned that, with L-dopa treatment, some dopamine-releasing neurons that aren't affected by Parkinson's will now release too much dopamine? I would be afraid of schizophrenia for example.

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86BillionFireflies t1_j2b1pvx wrote

That's what side effects are. Anytime you take psychoactive medications, they're going to mess with a thousand different brain systems that ALSO happen to use the neurotransmitter(s) affected by the drug, but were functioning normally. Thankfully, the brain is usually pretty good at compensating for stuff like that (which is why drug tolerance is a thing). Otherwise, side effects would probably be a LOT worse in general.

But when you say you're worried about schizophrenia, that's still thinking about it wrong. Schizophrenia is not caused by a simple overabundance of dopamine, it's caused by some kind of complex disturbance in the activity of one or more networks of brain circuits. The fact that some of those circuits have some dopaminergic components, and that some of the drugs that can partially alleviate symptoms affect dopamine among other neurotransmitters does not make dopamine central to schizophrenia.

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