Fluoxetine partly exerts its actions through GABA: a neurochemical evidence

Neurochem Res. 2007 Sep;32(9):1559-65. doi: 10.1007/s11064-007-9357-2. Epub 2007 May 8.


Fluoxetine, as a serotonin re-uptake inhibitor augments serotonin concentration within the synapse by inhibiting the serotonin transporter. The contribution of amino acids has also been shown in depression. We hypothesized that fluoxetine exerts its actions at least in part by intervening brain signaling operated by amino acid transmitters. Therefore the aim of this study is to supply neurochemical evidence that fluoxetine produces changes in amino acids in cerebrospinal fluid of rats. Sprague-Dawley rats were anesthetized and concentric microdialysis probes were implanted stereotaxically into the right lateral ventricle. Intraperitoneal fluoxetine (2.5 or 5 mg/kg) or physiological saline was administered and the probes were perfused with artificial cerebrospinal fluid at a rate of 1 mul/min. In the chronic fluoxetine group, the rats were treated daily with oral fluoxetine solution or inert syrup for 3 weeks. The microdialysis probes were placed on the 21st day and perfused the next day. Fluoxetine was ineffective in changing the cerebrospinal fluid GABA levels at the dose of 2.5 mg/kg but produced a significant increase in the perfusates following injection of 5 mg/kg of fluoxetine (P < 0.05). Oral fluoxetine administration (5 mg/kg) for 21 days also elevated the CSF GABA levels by approximately 2-fold (P < 0.05). L: -glutamic acid levels were not affected in all groups. 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.

MeSH terms

  • Animals
  • Fluoxetine / administration & dosage
  • Fluoxetine / pharmacology*
  • Glutamic Acid / cerebrospinal fluid
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • gamma-Aminobutyric Acid / cerebrospinal fluid
  • gamma-Aminobutyric Acid / physiology*


  • Fluoxetine
  • Glutamic Acid
  • gamma-Aminobutyric Acid