Central actions of serotonin and fluoxetine on the QT interval of the electrocardiogram in trout

QT interval of the electrocardiogram (ECG) is a measure of the duration of the ventricular depolarization and repolarization. In humans, prolongation of the QT interval is a known clinical risk factor for the development of ventricular arrhythmias including 'Torsades de Pointes' and possible sudden cardiac death. After oral administration, fluoxetine (FLX), as well as other selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors can affect cardiac autonomic control, including the QT interval. However, the action of centrally administered FLX on the QT interval has never been explored. Consequently, using the unanesthetized trout as an animal model, we sought to compare the effects of intracerebroventricular (ICV) injection of FLX (5, 15 or 25 µg) on the QT interval of the ECG with the effects observed following ICV injection of 5-HT (0.05, 0.5 or 5 nmol). The QT interval was corrected for the R-R interval. The highest doses of centrally administered FLX and 5-HT induced a prolongation of the corrected QT (QTc) interval reaching a maximum value of 5-10 min after injection (+8% and +6% respectively, P < 0.05). The intra-arterial (IA) injections of 5-HT and FLX were without significant effect on the QTc. The IA injection of blockers of the autonomic nervous system indicated that the sympathetic nervous system modulated the QTc interval. In conclusion, our data demonstrate that for the first time in any animal species, cardiac electrophysiology is sensitive to central 5-HT and that FLX within the brain may disrupt the autonomic control of ventricular repolarization.