Possible Interaction: Fluoxetine and Gamma-Aminobutyric Acid

“We observed that FLX robustly decreases both glutamatergic and gamma-Aminobutyric acid (GABA)-ergic synaptic release in a SERT-independent manner.”

“There is a wealth of evidence from animal models that fluoxetine specifically, and SSRIs in general, can increase the potential for activity-dependent plasticity in the adult brain, most probably through a reduction of extracellular concentrations of GABA and an increase in BDNF expression.”

“ Oral fluoxetine administration (5 mg/kg) for 21 days also elevated the CSF GABA levels by approximately 2-fold (P < 0.05).”

“These neurochemical findings show that fluoxetine , a selective serotonin re-uptake inhibitor affects brain GABA levels indirectly, and our results suggest that acute or chronic effects may be involved in beneficial and/or adverse effects of the drug.”

“At concentrations above 10 μM fluoxetine inhibited the binding of both [3H]GABA (IC50 = 2 mM) and [3H]flunitrazepam (IC50 = 132 μM ) to the GABAA receptor complex in brain cortical membranes.”

“ Fluoxetine increased the response of the receptor to submaximal GABA concentrations but did not alter the maximum current amplitude.”

“This suggests that fluoxetine acts through a novel modulatory site on the GABAR.”

“Carbamazepine and fluoxetine significantly increased GABA and reduced glutamate levels in both brain areas.”