Cardiovascular alterations and autonomic imbalance in an experimental model of depression

Abstract

Depressed patients with and without a history of cardiovascular pathology display signs, such as elevated heart rate, decreased heart rate variability, and increased physiological reactivity to environmental stressors, which may indicate a predisposition to cardiovascular disease. The specific physiological mechanisms associating depression with such altered cardiovascular parameters are presently unclear. The current study investigated cardiovascular regulation in the chronic mild stress rodent model of depression and examined the specific autonomic nervous system mechanisms underlying the responses. Sprague-Dawley rats exposed to a series of mild, unpredictable stressors over 4 wk displayed anhedonia (an essential feature of human depression), along with elevated resting heart rate, decreased heart rate variability, and exaggerated pressor and heart rate responses to air jet stress. Results obtained from experiments studying autonomic blockade suggest that cardiovascular alterations in the chronic mild stress model are mediated by elevated sympathetic tone to the heart. The present findings have implications for the study of pathophysiological links between affective disorders and cardiovascular disease.

Evaluation of Baroreceptor Reflex Function in the Chronic Mild Stress Rodent Model of Depression

“…Similar to previous studies from our laboratory and others (22)(23)(24), the CMS group displayed a significant reduction in sucrose intake and sucrose preference following 4 weeks of CMS, indicative of the reduced responsiveness to pleasurable stimuli (i.e., anhedonia) often observed in human depression. The reduction in sucrose consumption is a direct result of CMS, as the CMS group did not alter its water intake during the study and it did not differ in body weight from the control group.…”

“…The CMS procedure employed here was designed to maximize the unpredictable nature of the stressors while minimizing pain and discomfort; details of this procedure, including reliability and validity of the model, have been described in detail elsewhere (19,20,23,27). Briefly, the CMS group was exposed to the following stressors in a randomized fashion during a one-week period: continuous overnight illumination (two 12-hour periods), 40°c age tilt (one 7-hour period), paired housing (one 16-hour period and one 20-hour period), damp bedding (300 ml water spilled onto bedding; one 16-hour period), acute water deprivation (one 16-hour period) exposure to an empty water bottle immediately following the period of acute water deprivation (one 1-hour period), stroboscopic illumination (300 flashes/minute; one 6-hour period and one 4-hour period), and continuous white noise (approx.…”

“…The methods for acute sucrose preference tests, used to operationally define anhedonia, have been described previously (23,24). Anhedonia was defined specifically as a reduction in sucrose intake and sucrose preference relative to the control group and baseline values.…”

“…This model is a widely studied, valid, and reliable animal analog of depression, and has been shown to produce several behavioral changes that mirror the mood disorder (19)(20)(21)(22). In addition to its utility for investigating depression-relevant behaviors, our laboratory has demonstrated that CMS is a useful model for studying cardiovascular changes associated with depression and potential causal and common mechanisms that underlie the association of depression and cardiovascular disease (23)(24)(25)(26).…”

“…For instance, CMS in rats has been shown to produce elevated resting HR, reduced resting HR variability, exaggerated pressor and HR responses to a novel acute stressor, sympathoexcitation, and increased susceptibility to ventricular arrhythmias (23,24,26).…”