Metyrapone and fluoxetine suppress enduring behavioral but not cardiac effects of subchronic stress in rats

Carnevali, Luca, Bondarenko, Evgeny, Sgoifo, Andrea, Walker, Frederick R., Head, Geoffrey A., Lukoshkova, Elena V., Day, Trevor A. and Nalivaiko, Eugene 2011, Metyrapone and fluoxetine suppress enduring behavioral but not cardiac effects of subchronic stress in rats, American journal of physiology : regulatory, integrative and comparative physiology, vol. 301, no. 4, pp. R1123-R1131.

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Title Metyrapone and fluoxetine suppress enduring behavioral but not cardiac effects of subchronic stress in rats
Author(s) Carnevali, Luca
Bondarenko, Evgeny
Sgoifo, Andrea
Walker, Frederick R.
Head, Geoffrey A.
Lukoshkova, Elena V.
Day, Trevor A.
Nalivaiko, Eugene
Journal name American journal of physiology : regulatory, integrative and comparative physiology
Volume number 301
Issue number 4
Start page R1123
End page R1131
Total pages 9
Publisher American Physiological Society
Place of publication Bethesda, Md.
Publication date 2011-10
ISSN 0363-6119
Keyword(s) circadian
heart rate
psychological stress
vagal rebound
Summary In humans, chronic stressors have long been recognized as potential causes for cardiac dysregulation. Despite this, the underlying mechanistic links responsible for this association are still poorly understood. The purpose of this study was to determine whether exposure to a paradigm of subchronic stress can provoke enduring changes on the heart rate of experimental rats and, if so, to reveal the autonomic and neural mechanisms that mediate these effects. The study was conducted on adult male Sprague-Dawley rats instrumented for telemetric recording of heart rate and locomotor activity. Animals were submitted to a subchronic stress protocol, consisting of a 1-h foot shock session on five consecutive days. Heart rate and locomotor activity were recorded continuously for 3 days before and for 6 days after the subchronic stress period. Subchronic foot shock produced significant and enduring reduction in heart rate both during the dark/active [Δ= −23 ± 3 beats per minute (bpm)] and light/inactive (Δ= −20 ± 3 bpm) phases of the circadian cycle, and a reduction in locomotor activity during the dark/active phase [Δ= −54 ± 6 counts per hour (cph)]. The bradycardic effect of subchronic stress was not related to a reduced locomotion. Selective sympathetic (atenolol) and vagal (methyl-scopolamine) blockades were performed to reveal which autonomic component was responsible for this effect. We found that the fall in heart rate persisted after subchronic stress in animals treated with atenolol (active phase Δ= −16 ± 3 bpm, inactive phase Δ= −19 ± 2 bpm), whereas vagal blockade with scopolamine transiently prevented this effect, suggesting that the bradycardia following subchronic stress was predominantly vagally mediated. Fluoxetine (selective serotonin reuptake inhibitor) and metyrapone (inhibitor of corticosterone synthesis) treatments did not affect heart rate changes but prevented the reduction in locomotion. We conclude that subchronic stress exposure in rats reduces heart rate via a rebound in vagal activation and that this effect is serotonin- and corticosterone-independent.
Language eng
Field of Research 069999 Biological Sciences not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2011, American Physiological Society
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Document type: Journal Article
Collection: Faculty of Science, Engineering and Built Environment
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