Mechanisms underlying altered mood and cardiovascular dysfunction: the value of neurobiological and behavioral research with animal models

Abstract

A bidirectional association between mood disorders and cardiovascular diseases has been described in humans, yet the precise neurobiological mechanisms that underlie this association are not fully understood. This article is focused on neurobiological processes and mediators in mood and cardiovascular disorders, with an emphasis on common mechanisms including stressor reactivity, neuroendocrine and neurohumoral changes, immune alterations, autonomic and cardiovascular dysregulation, and central neurotransmitter and neuropeptide dysfunction. A discussion of the utility of experimental investigations with rodent models, including those in rats and prairie voles (Microtus ochrogaster), is presented. Specific studies using these models are reviewed, focusing on the analysis of behavioral, physiological and neural mechanisms underlying depressive disorders and cardiovascular disease. Considered in combination with studies using human samples, the investigation of mechanisms underlying depressive behaviors and cardiovascular regulation using animal models will enhance our understanding of the association of depression and cardiovascular disease, and will promote the development of improved interventions for individuals with these detrimental disorders.

Figure 1

Example of a chronic mild stress paradigm. Reprinted from (Grippo et al., 2006); permission requested.

Figure 2

Mean (+ SEM) absolute water and sucrose consumption (Panel A) and percent preference for sucrose (relative to total fluid intake; Panel B) during a 1-hour fluid intake test in chronic mild stress (CMS) and control groups at baseline and during 4 weeks of CMS. The groups did not differ in the amount of absolute fluid intake or sucrose preference during the baseline period. Following 4 weeks of CMS, the CMS group consumed significantly less sucrose, and showed a significantly reduced sucrose preference, versus the baseline period and the control group (*P < 0.05 vs. control group at the same time point; ^#P < 0.05 vs. respective baseline value). Modified from (Grippo et al., 2002); permission requested.

Figure 3

Mean (+ SEM) time to onset of premature ventricular contractions (PVC), bigeminy, salvos, ventricular tachycardia (VT) and ventricular fibrillation (VF) following intravenous aconitine administration (5 μg/kg/min) following 4 weeks of chronic mild stress (CMS) or undisturbed control conditions. CMS reduced the onset time to PVC, salvo and VT (*P < 0.05 vs. respective control value). Modified from (Grippo et al., 2004), with permission, copyright 2004 American Physiological Society.

Figure 4

Mean (+ SEM) water and sucrose intake in female prairie voles during a 1-hour fluid intake test at baseline and following 2 and 4 weeks of isolation or pairing (Panel A), and amount of time spent struggling, climbing, swimming and immobile during a 5-minute forced swim test following 4 weeks of isolation or pairing (Panel B). Social isolation reduced sucrose intake and increased immobility time in the forced swim test (*P < 0.05 vs. respective paired value; ^#P < 0.05 vs. respective baseline value). Modified from (Grippo et al., 2008b); permission requested.

Figure 5

Mean (+ SEM) heart rate (Panel A), standard deviation of normal-to-normal intervals (SDNN index; Panel B), and amplitude of respiratory sinus arrhythmia (Panel C) in prairie voles at baseline and following 2 and 4 weeks of social isolation or pairing. Social isolation increased heart rate, and reduced SDNN index and respiratory sinus arrhythmia amplitude (*P < 0.05 vs. respective paired value; ^#P < 0.05 vs. respective baseline value). Reprinted from (Grippo et al., 2007b); permission requested.