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

Abstract

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.

Fish Oil, but Not Olive Oil, Ameliorates Depressive-Like Behavior and Gut Microbiota Dysbiosis in Rats under Chronic Mild Stress

“…The CMS model also resulted in lower body weight gain in the experimental rats than the control rats. Cavigelli et al demonstrated that four weeks of CMS reduced the body weight of rats [20]. Another study reported that six weeks of CMS significantly reduced body weight, and fluoxetine antidepressant treatment improved depressive-like behaviors without causing body weight gain [21].…”

Variability in PolyIC induced immune response: Implications for preclinical maternal immune activation models

“…As noted in Tables 2 and 3, the majority of cytokine levels increased between the 3 h and 6 h time points, even for the saline treated controls. Animals in the present study received multiple bouts of restraint and blood sample collection within 6 h, potentially inducing stress that may exacerbate cytokine response (Johnson et al, 2002; Cavigelli et al, 2018). Moreover, metabolic chambers, such as the CLAMS, have been associated with stress responses in rodents and may have contributed to the relatively high baseline cytokine levels in the saline group (Kalliokoski et al, 2013).…”

Priorities in stress research: a view from the U.S. National Institute of Mental Health

“…These changes do not impact the academic content of the article. and populations (Tractenberg et al, 2016;Bonapersona et al, 2019;Shields et al, 2017;Loi et al, 2017;Cavigelli et al, 2018), it is critically important to optimize experimental designs to address the specific experimental questions.…”