title: 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 (15s 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 (1mg/kg, sc). Atomoxetine decreased (p<0.05) baseline mBP from 128+/-11 mm Hg (mean+/-SD) to 117+/-19 mm Hg; baseline HR slowed from 380+/-23 bpm to 351+/-21 bpm. The mBP increase to acute stress was similar after saline vs. after drug, but the peak was attained more slowly. After atomoxetine HR tended to slow during stress rather than accelerate. In Protocol 2 the cardiovascular responses were tested (n=6) for 3 days post-saline and for 3 days after a higher dose of atomoxetine (2mg/kg, sc). The average HR acceleration during the last 10s 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.
authors.affiliation: Math, Science and Technology Center at Dunbar High School, Lexington, KY, USA.
authors.forename: Winston Y
authors.initials: WY
authors.lastname: Li
authors.forename: Shara E
authors.initials: SE
authors.lastname: Strang
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
authors.forename: Re'gie
authors.initials: R
authors.lastname: Smith
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Silcox
authors.forename: Sheng-Gang
authors.initials: SG
authors.lastname: Li
authors.forename: Bobby R
authors.initials: BR
authors.lastname: Baldridge
authors.forename: K Paul
authors.initials: KP
authors.lastname: Nesselroade
authors.forename: David C
authors.initials: DC
authors.lastname: Randall
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000188:drug therapy* / Q000209:etiology; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D011437:Propylamines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications / Q000209:etiology; D013610:Tachycardia / Q000188:drug therapy* / Q000209:etiology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride