Prozac(fluoxetine) is used to treat a broad range of mental disorders(depressive,panic

disorder,post-traumatic stress disorder, OCD). In addition to delaying the reuptake of

serotonin, it has a binding affinity for many receptors (acetylcholine, adrenergic, dopamine
etc). Trying to find an affinity of this popular ssri with GABA receptors(any form) as a possible
extra mechanism of action, i came across this pubmed article (http://www.ncbi.nlm.nih.gov/
pmc/articles/PMC4307650/). This study suggests that there are large gaps in our
understanding of the relationship between GABA and major depressive disorder. Although if
you look closely at each paragraph you will see that there is evidence of this mental disorder
lowering gaba concentrations in some parts of the brain (occipital cortex, prefrontal cortex,
frontal cortex).
About fluoxetine and GABA neurotransmission, it states that there is a fair amount data that
fluoxetine has the ability to POSITIVE MODULATE GABA neurotransmission
INDEPENDENTLY OF SEROTONERGIC SIGNALING.
What i find more interesting thought is this: Several studies have demonstrated that
antidepressant treatments, such as the SSRI fluoxetine, can enhance the production of such
neurosteroids as allopregnanolone. For example, preclinical models have demonstrated that
acute intraperitoneal administration of 20 mg/kg fluoxetine significantly elevates the brain
concentration of allopregnanolone in adrenalectomized, castrated male rats 30 minutes after
injection,78 which may suggest that fluoxetine treatment can indirectly modulate GABAA
receptor-mediated neurotransmission.
and this :
However, a separate research group presented another small but better-controlled study, 83
which found that a small sample of treatment-nave outpatients with MDD had altered
plasma neurosteroid concentrations compared to healthy controls. Specifically,
allopregnanolone and 3,5-tetrahydroprogesterone were significantly reduced in patients
compared to healthy control subjects, while 3,5-tetrahydroprogesterone was significantly
increased. These differences were reversed by chronic treatment with fluoxetine. In another
experiment presented in the same paper, the authors found similar but much smaller
responses in neurosteroid concentrations to successful antidepressant treatments in a more
severely depressed sample of patients.

One of the keys to successful treatment of depression with prozac is an allosteric modulation
of GABA receptor with ALLOPREGNANOLONE. If this is a fact then why not using
allopregnanolone directly as a mood enhancer drug. To my surprise allopregnanolone is
under development by Sage therapeutics as an intravenous drug for the treatment of
postpartum depression and seizures.

Maybe this type of estrogen activity is also responsible for the food cravings,
especially for high caloric foods when you are under treatment with prozac or other
ssri.
(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332196/)