Electrophysiological effect of fluoxetine on Xenopus oocytes heterolo- gously expressing human serotonin transporter

Aim： To investigate the electrophysiological effect of fluoxetine on serotonin transporter. Methods： A heterologous expression system was used to introduce human serotonin transporter （hSERT） into Xenopus oocytes. A 2-electrode voltage clamp technique was used to study the pharmacological properties of fluoxetine. Results： hSERT-expressing oocytes were perfused with 10 μnol/L serotonin （5-HT） to induce hSERT-current. The 5-HT-induced hSERT currents were dose-dependently reversed by fluoxetine. The RC50 （concentration that achieved a 50% reversal） was approximately 3.12 μnol/L. Fluoxetine took more time to combine with hSERT than 5-HT did, and it was also slow to dissociate from hSERT. This long-lasting effect of fluoxetine affected normal 5-HT transport. Fluoxetine significantly prolonged the time constant for 5-HT-induced hSERT current. These results might be used to explain the long-lasting anti-anxiety effect of fluoxetine in clinical practice, because it increases the concentration of 5-HT in the synaptic cleft by its enduring suppression of the function of 5-HT transporters. Conclusion： Fluoxetine inhibits 5-HT reuptake by competing with 5-HT and changing the normal dynamics of hSERT.