Atomoxetine changes rat's HR response to stress from tachycardia to bradycardia via alterations in autonomic function

Abstract Atomoxetine is a central norepinephrine reuptake inhibitor used to treat attention deficit hyperactivity disorder. We tested the effects of atomoxetine upon the heart rate (HR) and mean arterial blood pressure (mBP) response to aversive conditioning. In Protocol 1 the mBP and HR responses to a stress (15 s tone followed by shock) were tested in 8 Sprague–Dawley rats given saline pretreatment for 3 days; the rats' responses were then tested for 3 additional days following atomoxetine (1 mg/kg, sc). Atomoxetine decreased ( p n  =  6) for 3 days post-saline and for 3 days after a higher dose of atomoxetine (2 mg/kg, sc). The average HR acceleration during the last 10 s of the stress after saline (+ 7.5 ± 14.7 bpm) was replaced by a HR slowing (− 6.2 ± 10.5 bpm). We conclude that drug treatment (a) decreases baseline sympathetic tone and/or elevates cardiac parasympathetic tone; (b) slows sympathetic arousal to acute stress without changing its magnitude; and, (c) enables the emergence of elevated parasympathetic tone during the stress. These autonomic consequences are consistent with atomoxetine's anxiolytic and transient sedative effects.