What exactly is the mechanism of action of Fluoxetine/Prozac?

Question

I have read that it works by stopping the reuptake of the neurotransmiter serotonin but I have also heard that it actually encourages the growth more neuroreceptors. Its hard to seperate fact from fiction. It also may be possible that the chemists themselves don't know. In any case if you have any information on the matter i would be appreciated.

Answer 1

Prozac also causes increased glucocorticoid receptors in the hippocampus, this is part of the HPA axis feedback system. As cortisol is a glucocorticoid these receptors are a negative feedback system; thus preventing the release of more ACTH. Less CRH = Less ACTH = Less Cortisol = Less stress. More glucocorticoid receptors = Less CRH.

Answer 2

You're right, the MOA is exactly as you posited, i.e. inhibition of pre-synaptic reuptake of 5-HT, however this doesn't quite explain the whole story.  There is evidence of upregulation of post-synaptic receptors as you mentioned... Irrespective of this, it's still unclear why it takes Fluoxetine and essentially all SSRIs weeks before they begin to relieve the symptoms of the underlying disease, so we still don't have a "complete" understanding of exactly how fluoxetine works at every level.