Serotonin and Dopamine: Do Both Matter?

Right Brain Bio was born when I found a question about Parkinson’s that couldn’t be answered by the scientific literature: if Parkinson’s were a disease of dopamine deficiency, then why doesn’t dopamine replacement fix the disease?

With greater understanding that serotonin – a neurotransmitter chemically related to dopamine that is also affected by Parkinson’s disease (PD) – affects mood, the sleep-wake cycle and risk for constipation, I wondered. Could serotonin abnormalities be another target for treating the disease?

In reading about serotonin in PD, another question arose that couldn’t be answered by the scientific literature: why are dopamine abnormalities are more pronounced in the putamen than the caudate, but serotonin abnormalities are more pronounced in the caudate than in the putamen? (For those of you who don’t study brain anatomy, the caudate and putamen are two brain regions that control movement and that are most affected by PD.)

Why focus on differences between dopamine and serotonin?

The answer to the question from perplexity.ai is the same as what I found in the literature: the abnormalities for each of dopamine and serotonin are caused by those neurons being affected differently in PD. This feels as though the message is that the abnormality is the result of the abnormality. Very unsatisfying.

Here’s a standard approach to define whether there is a path forward for serotonin-directed therapy development: 1. confirm that the differential effects on dopamine and serotonin are relevant to the disease, 2. pinpoint the biologic mechanisms that could be the cause(s), 3. identify studies relevant to PD directed at those mechanisms that confirm their relevance and 4. conduct studies to validate which mechanism(s) is/are worth further pursuit.

If we could confirm that the differential effects on dopamine and serotonin are relevant to the disease and understand the biologic mechanisms that are the cause(s), then that could confirm additional opportunities to treat the disease, perhaps in this case to reverse the mood, sleep-wake and/or gastrointestinal manifestations of the disease.

We’ll share here what we learn.