Review
Rodent models of depression-cardiovascular comorbidity: Bridging the known to the new

https://doi.org/10.1016/j.neubiorev.2016.11.006Get rights and content

Highlights

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    Depression-cardiovascular comorbidity is a relevant clinical issue.

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    Rodent models have been developed for investigating mechanisms and processes linking co-occurring mood and cardiovascular disorders.

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    Factors and potential pathophysiological mechanisms that influence the co-occurrence of a depressive-like state and an increased cardiovascular risk in rodents are summarized and discussed.

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    An up-to-date reference of the experimental evidence gathered so far from rodent models of depression and cardiovascular disorders.

Abstract

Numerous epidemiological studies have demonstrated a close and bidirectional association between depression and cardiovascular disorders (CVD). This comorbidity places a significant burden on individuals and the healthcare system. Not surprisingly, in the last two decades preclinical research in the field of depression and CVD has rapidly progressed. Multiple studies have demonstrated that aspects of human depression/cardiovascular comorbidity can be modeled in rodents exposed to chronic stress paradigms and that a depressive-like syndrome can be induced in rodent models of CVD. This research has provided insights into neural, autonomic, humoral, immune and circulatory mechanisms linking co-occurring mood and CVD. Recent investigations have started to address gender and individual differences in the vulnerability to both disorders and have begun to explore the efficacy of novel pharmacological interventions for the treatment of these comorbid conditions. This review discusses relatively well-established findings and the latest discoveries from rodent models of depression and CVD, with the aim of providing an up-to-date reference which may guide future studies of the relationship between mood and cardiovascular disturbances.

Introduction

“Depression can break your heart”. This was the title of a fact sheet written in 2001 by The National Institute of Mental Health and National Heart Lung and Blood Institute in the wave of a decade of research demonstrating a clear link between depression and cardiovascular disorders (CVD) (National Institute of Mental Health, 2001). Since then not only has a great deal of clinical evidence accumulated in support of this comorbidity but also numerous animal models have been developed in an attempt to reveal basic mechanisms and processes linking co-occurring mood and cardiovascular disorders. It is clear from these studies that depressive-like symptoms and cardiovascular abnormalities can be reliably reproduced in rodent models of chronic stress, and that a depressive-like syndrome can be provoked in rodent models of CVD. Mechanistic investigations have revealed a number of neural, autonomic, humoral, immune and circulatory pathways that could potentially mediate the association between depression and CVD. Moreover, recent work has started to tackle the issue of gender and individual differences in the vulnerability to both conditions, which is a necessary step towards a successful translation of experimental data into clinic. Finally, rodent studies have evaluated the efficacy of conventional antidepressant treatments also in terms of cardioprotection/cardiotoxicity, as well as the potential utility of novel pharmacological interventions for the treatment of these comorbid conditions. The purpose of this review is to integrate relatively well-established findings with the latest discoveries obtained from rodent models of depression and cardiovascular comorbidity, thereby providing an up-to-date reference of the experimental evidence on the relationship between mood and cardiovascular disorders.

Section snippets

Comorbidity between depression and cardiovascular disorders

It is quite remarkable that depression is projected to become the leading cause of worldwide disability by 2030 (Mathers et al., 2008). A substantial part of this burden relates to its association with medical illnesses, particularly CVD. Since the landmark study by Frasure-Smith and colleagues in 1993 demonstrating that depression is an independent risk factor for death at six months after myocardial infarction (Frasure-Smith et al., 1993), dozens of epidemiological studies have examined the

Rodent models of depression and cardiovascular comorbidity

In combination with findings from human studies, the use of well-validated, reliable, and relevant preclinical models offers several advantages for the study of the comorbidity between depression and CVD. Research using animal models allows for a high level of experimental control as well as integrative methods and analyses. Given the established stress dependence of both diseases, rodent research has implemented stress paradigms for investigating common and causal pathophysiological mechanisms

Conclusion

The comorbidity between depression and CVD places a significant burden on individuals and the healthcare system. Over the past two decades rodent research has systematically attempted to study this association. Rodent models of chronic stress and CVD have enhanced our understanding of the link between emotion and cardiovascular regulation by providing greater insight into neuronal, autonomic, humoral, immune and circulatory mechanisms that may contribute to the pathogenesis of both depression

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