Timing matters: the interval between acute stressors within chronic mild stress modifies behavioral and physiologic stress responses in male rats

• Published in: Stress (Amsterdam, Netherlands) Netherlands), 2018-09, Vol.21 (5), p.453-463
• Main Authors: Cavigelli, Sonia A, Bao, Alexander D, Bourne, Rebecca A, Caruso, Michael J, Caulfield, Jasmine I, Chen, Mary, Smyth, Joshua M
• Format: Article
• Language: English
• Subjects: Animals; Body Weight - physiology; Corticosterone - blood; Male; Rats; Rats, Sprague-Dawley; Stress, Physiological - physiology; Stress, Psychological - blood; Stress, Psychological - physiopathology; Time Factors
• ISSN: 1025-3890; 1607-8888
• DOI: 10.1080/10253890.2018.1459557

Chronic mild stress can lead to negative health outcomes. Frequency, duration, and intensity of acute stressors can affect health-related processes. We tested whether the temporal pattern of daily acute stressors (clustered or dispersed across the day) affects depression-related physiology. We used a rodent model to keep stressor frequency, duration, and intensity constant, and experimentally manipulated the temporal pattern of acute stressors delivered during the active phase of the day. Adult male Sprague-Dawley rats were exposed to one of three chronic mild stress groups: Clustered: stressors that occurred within 1 hour of each other (n = 21), Dispersed: stressors that were spread out across the active phase (n = 21), and Control: no stressors presented (n = 21). Acute mild stressors included noise, strobe lights, novel cage, cage tilt, wet bedding, and water immersion. Depression-related outcomes included: sucrose preference, body weight, circulating glucocorticoid (corticosterone) concentration after a novel acute stressor and during basal morning and evening times, and endotoxin-induced circulating interleukin-6 concentrations. Compared to control rats, those in the Clustered group gained less weight, consumed less sucrose, had a blunted acute corticosterone response, and an accentuated acute interleukin-6 response. Rats in the Dispersed group had an attenuated corticosterone decline during the active period and after an acute stressor compared to the Control group. During a chronic mild stress experience, the temporal distribution of daily acute stressors affected health-related physiologic processes. Regular exposure to daily stressors in rapid succession may predict more depression-related symptoms, whereas exposure to stressors dispersed throughout the day may predict diminished glucocorticoid negative feedback.