Aim: 

The aim was to test whether stress-induced cardiac arrhythmias could be suppressed by systemic administration of 8-hydroxy-2-(di-n-propylamino)tertraline (8-OH-DPAT), a 5-HT_1A agonist with central sympatholytic properties.

Methods: 

Adult male rats were implanted with radiotransmitters for ECG, body temperature (T) and locomotor activity (Act) recordings. In the first experiment, rats were exposed to 15-min social defeat test, after either vehicle or 8-OH-DPAT (100 mg/kg s.c.) injection. In the second experiment, prior to vehicle/8-OH-DPAT administration, animals were injected with zatebradine (a pacemaker current blocker) to produce sinus bradycardia.

Results: 

8-OH-DPAT caused bradycardia and increase in Act, besides the expected hypothermic effect. Subjecting vehicle-treated animals to social defeat caused increase in heart rate, Act and T, and the occurrence of ventricular and supraventricular premature beats; all these effects were profoundly attenuated by 8-OH-DPAT. Zatebradine provoked a robust decrease of heart rate, that was not further modified by 8-OH-DPAT. In zatebradine/vehicle-treated rats, the incidence of ventricular and supraventricular arrhythmias during defeat was increased (2.5-fold and 3.5-fold, respectively) as compared to vehicle-treated rats. 8-OH-DPAT administered after zatebradine reduced significantly the occurrence of stress-induced arrhythmic events.

Conclusions: 

(i) pharmacologically-induced reduction of heart rate (via zatebradine) resulted in an increased susceptibility to stress-induced cardiac arrhythmias, possibly due to the prolongation of the ventricular diastolic period; (ii) systemic administration of the 5-HT_1A agonist (8-OH-DPAT) abolished these arrhythmic events, likely by suppressing stress-induced cardiac sympathetic outflow.