I have a knowledge gap which I can't find many papers about.

I know that receptors like 5HT desensitize when a prolonged increased1 availability is present because the brain tries to maintain homeostatic equilibrium. This might happen because of the use of SSRIs as

Presynaptic 5-HT1ARs readily desensitise following exposure to increased 5-HT availability (e.g. through chronic selective serotonin reuptake inhibitors (SSRIs)) but postsynaptic 5-HT1ARs do not - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606297/

Now my question is what happens if SSRIs merely normalize a 5HT availability deficit? Suppose for whatever reason an individual has less available2 Serotonin but a normal3 baseline receptor density i.e. a balanced 5HT saturation.

Would 5HT neccesarily downregulate if SSRIs were to increase 5HT availability to a normal level needed to maintain homeostatic equilibrium between receptor density and availability?

1 - = higher than normal

2 - e.g. because of insufficient release or production or whatever condition that causes lower than normal availability
3 - not down / up regulated



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