Nicotinic acetylcholine receptor antagonist effect of fluoxetine in rat hippocampal slices

We compared the effect of mecamylamine and fluoxetine on the hippocampal noradrenaline (NA) release evoked by nicotine in vitro. Nicotine (100 mu M) increased the basal release of [H-3]NA from rat hippocampal slices. This effect was blocked by the potent nicotinic antagonist mecamylamine in a dose-dependent manner (IC50 = 0.19 mu M). The selective serotonin reuptake inhibitor (SSRI) fluoxetine also antagonised the response to nicotine in a dose-dependent manner with a similar strength (IC50 = 0.57 mu M). Our data indicate that fluoxetine has nicotinic acetylcholine receptor antagonist effect in the central nervous system. The possible clinical significance of this finding is discussed.