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

From the Departments of Psychology (A.J.G., J.A.M., A.K.J.), Integrative Physiology (A.K.J.), and Pharmacology (A.K.J.), and the Cardiovascular Center (A.J.G., J.A.M., A.K.J.), University of Iowa, Iowa City, Iowa.

Address correspondence and reprint requests to Alan Kim Johnson, PhD, Department of Psychology, University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242-1407. E-mail: alan-johnson{at}uiowa.edu

Objective: There is a bidirectional relationship between mood disorders (e.g., depression) and altered cardiovascular regulation (e.g., heart disease); however, the precise causal and/or common mechanisms underlying this association are unclear. In previous studies, we have noted indications of altered sympathetic drive to the heart in rats that exhibit anhedonia, an operational sign of depression induced by subjecting the animals to a series of mild and unpredictable stressors (chronic mild stress (CMS) rodent model of depression). The purpose of the present study was to more fully characterize baroreceptor reflex function in rats with experimentally induced depression.

Methods: Male, Sprague-Dawley rats were exposed to either 4 weeks of mild, unpredictable stressors (CMS group) or standard housing conditions (control group). Depression-like behavior, resting hemodynamic and cardiac parameters, and baroreceptor reflex function were investigated in all animals after the CMS period.

Results: CMS produced anhedonia, evidenced by reduced sucrose intake and sucrose preference, as well as elevated resting heart rate (HR), slightly elevated blood pressure, and reduced HR variability. These animals also exhibited significantly attenuated sympathoexcitatory responses to hypotension, and an elevation of basal sympathetic nerve activity.

Conclusions: These findings suggest that CMS is associated with altered sympathoexcitatory responses after baroreceptor unloading and provide further insights into potential common mechanisms underlying the association of depression and altered cardiovascular control.

Key Words: autonomic nervous system • baroreflex • cardiovascular • heart rate variability • lumbar sympathetic nervous system activity • mood disorders

Abbreviations: ANOVA = analysis of variance; CMS = chronic mild stress; DSM-IV-TR = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision; HR = heart rate; LSNA = lumbar sympathetic nerve activity; MAP = mean arterial pressure; SEM = standard error of the mean; SDNN = standard deviation of normal-to-normal intervals.