8-OH-DPAT prevents cardiac arrhythmias and attenuates tachycardia during social stress in rats

Abstract

The aim of this study was to apply a behavioural stress paradigm for studying the neural mechanisms underlying stress-induced arrhythmias, and to test whether such arrhythmias could be suppressed by systemic administration of 8-OH-DPAT, a 5-HT1A agonist possessing central sympatholytic properties. The study was conducted on adult male rats instrumented for telemetric recordings of ECG, body temperature and locomotor activity. In the first experiment, rats were subjected to social defeat after either 8-OH-DPAT (100 µg/kg s.c.) or vehicle injection. In the second experiment, prior to vehicle/8-OH-DPAT administration, animals were pre-treated with zatebradine, a blocker of the pacemaker current. 8-OH-DPAT caused prolongation of basal RR interval, increase in locomotion and hypothermia. Subjecting vehicle-treated animals to social defeat caused shortening in RR interval, increase in locomotor activity and hyperthermia, and provoked the occurrence of premature ventricular and supraventricular beats; all these effects were substantially attenuated by 8-OH-DPAT. Zatebradine caused prolongation of RR interval. In zatebradine/vehicle-treated rats, the incidence of ventricular and supraventricular premature beats during defeat increased 2.5-fold and 3.5-fold, respectively. 8-OH-DPAT administered after zatebradine significantly reduced these stress-induced arrhythmias. We conclude that: i) pharmacologically induced prolongation of RR interval may contribute to an increased susceptibility to stress-induced cardiac arrhythmias, possibly due to the prolongation of the ventricular diastolic period with restored excitability; and ii) systemic administration of 8-OH-DPAT abolishes these arrhythmic events, likely by suppressing stress-induced cardiac sympathetic outflow.