Differential acute effects of fluoxetine on frontal and auditory cortex networks in vitro

Primary cultures of neuronal networks grown on microelectrode arrays were used to quantify acute effects of fluoxetine (Prozac) on spontaneous spike and burst activity. For frontal cortex cultures, fluoxetine showed consistent inhibitory effects and terminated activity at 10-16 microM. IC(50) mean+/-S.E. for spike rates was 5.4+/-0.7 microM (n=15). For auditory cortex cultures, fluoxetine caused excitation at 1-10 microM, initial inhibition at 15 microM, and activity cessation at 20-25 microM. The spike rate IC(50) was 15.9+/-1.0 microM (n=11). Fluoxetine did not change the action potential waveform shape. However, at high concentrations, it caused total cessation of spike activity on all channels. The inhibition caused by fluoxetine was reversible for both tissues. Based on the results, we conclude that cultures showed repeatable, concentration-dependent sensitivities to fluoxetine but demonstrated tissue-specific responses for frontal and auditory cortex networks. These responses may not be due to the interference with serotonin reuptake, but may be due to a secondary effect on ionic channels.