Vagal Withdrawal and Susceptibility to Cardiac Arrhythmias in Rats with High Trait Aggressiveness

Carnevali, Luca; Trombini, Mimosa; Porta, Alberto; Montano, Nicola; Boer, Sietse F. de; Sgoifo, Andrea

doi:10.1371/journal.pone.0068316

Cited by 39 publications

(49 citation statements)

References 44 publications

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“…The findings of increased aggressive behaviours in depressed mice are consistent with previous reports examining the effects of stress on aggression in adult rodents, primates and human (Carnevali et al 2013;Crombach and Elbert 2014;Howell et al 2013). The tube test may reveal significant differences in mice with altered motor function or impulsivity, or under conditions of social stress (Kalueff et al 2007), and was originally developed as a test of social hierarchy/dominance.…”

Section: Discussionsupporting

confidence: 91%

Enhanced Aggressive Behaviour in a Mouse Model of Depression

et al. 2014

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Depression is one of the most common chronic mental disorders, which is a leading cause of morbidity and mortality in patients. Depression often leads to offensive and defensive behaviours but the underlying mechanisms are not known. We propose that the aggressive behaviours in depression can be modelled in animal experiments. In this study, we successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm and detected aggressive and social dominance behaviours in rodents by resident/intruder test and social dominance tube test (SDTT), respectively. The CUMS-exposed mice showed increased defensive, offensive and aggressive behaviours in the resident-intruder test. In the SDTT, these mice showed enhanced social dominance. These alterations were associated with reduced MAP-2 expression in the hippocampus while no difference in β-tubulin expression was detected. In addition, the treatment of anti-depressant fluoxetine reversed the aggressive behaviours without reducing the social dominance behaviour induced by CUMS. However, fluoxetine did effectively reverted the changes in MAP-2 expression in the hippocampus. In addition, the nonspecific tricyclic antipsychotic drug, clozapine, reversed all symptoms of CUMS-exposed mice including aggressive tendencies, impulsive violence, social dominance behaviour and MAP-2 expression in the hippocampus. The results suggests that social maladjustment such as competition and social dominance are likely related to the dopaminergic system rather than the serotonergic system and the hippocampal dendritic structure protein MAP-2. Thus, dominance can be separated from aggression. This study shows that aggression/hostility and social hierarchy/dominance are increased in the CUMS-exposed mice and thus provide an excellent model for further study in the diagnosis and the treatment of depression-associated aggression.

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Section: Discussionsupporting

confidence: 91%

Enhanced Aggressive Behaviour in a Mouse Model of Depression

et al. 2014

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“…Indeed, a number of publications showed that HRV analysis works well in discriminating among different acute and chronic, environmental and social challenges, between aggressive and nonaggressive individuals, as well as in anxiety studies or studies on mutant mice (Carnevali et al, 2012a(Carnevali et al, , 2013(Carnevali et al, , 2014aCostoli et al, 2004Costoli et al, , 2005Sgoifo et al, 1997Sgoifo et al, , 2005.…”

Section: Animal Models Of Depression and Autonomic Imbalancementioning

confidence: 99%

Autonomic dysfunction and heart rate variability in depression

Sgoifo

Carnevali

Alfonso

et al. 2015

Stress

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254

160

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Depression occurs in people of all ages across all world regions; it is the second leading cause of disability and its global burden increased by 37.5% between 1990 and 2010. Autonomic changes are often found in altered mood states and appear to be a central biological substrate linking depression to a number of physical dysfunctions. Alterations of autonomic nervous system functioning that promotes vagal withdrawal are reflected in reductions of heart rate variability (HRV) indexes. Reduced HRV characterizes emotional dysregulation, decreased psychological flexibility and defective social engagement, which in turn are linked to prefrontal cortex hypoactivity. Altogether, these pieces of evidence support the idea that HRV might represent a useful endophenotype for psychological/physical comorbidities, and its routine application should be advised to assess the efficacy of prevention/intervention therapies in a number of psychosomatic and psychiatric dysfunctions. Further research, also making use of appropriate animal models, could provide a significant support to this point of view and possibly help to identify appropriate antidepressant therapies that do not interefere with physical health.

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“…Furthermore, when coping style was determined prior to chronic intermittent stress there was an association between passive coping and hypertension (Hawley et al, 2010). Alternatively, the cardiovascular responsivity of rats exhibiting either high or low aggression is also distinctly different; with high aggression rats displaying reduced vagal antagonism and increased tachyarrhythmias compared with non-aggressive rats (Carnevali et al, 2013a) Taken together, these studies indicate that the behavioral coping response is associated with cardiovascular susceptibility to stress.…”

Section: Role Of the Lc In Individual Differences In Cardiovascular Rmentioning

confidence: 99%

The brain norepinephrine system, stress and cardiovascular vulnerability

Wood

Valentino

2017

Neuroscience & Biobehavioral Reviews

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Chronic exposure to psychosocial stress has adverse effects on cardiovascular health, however the stress-sensitive neurocircuitry involved remains to be elucidated. The anatomical and physiological characteristics of the locus coeruleus (LC)-norepinephrine (NE) system position it to contribute to stress-induced cardiovascular disease. This review focuses on cardiovascular dysfunction produced by social stress and a major theme highlighted is that differences in coping strategy determine individual differences in social stress-induced cardiovascular vulnerability. The establishment of different coping strategies and cardiovascular vulnerability during repeated social stress has recently been shown to parallel a unique plasticity in LC afferent regulation, resulting in either excitatory or inhibitory input to the LC. This contrasting regulation of the LC would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The advances described suggest new directions for developing treatments and/or strategies for decreasing stress-induced cardiovascular vulnerability.

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Vagal Withdrawal and Susceptibility to Cardiac Arrhythmias in Rats with High Trait Aggressiveness

Cited by 39 publications

References 44 publications

Enhanced Aggressive Behaviour in a Mouse Model of Depression

Enhanced Aggressive Behaviour in a Mouse Model of Depression

Autonomic dysfunction and heart rate variability in depression

The brain norepinephrine system, stress and cardiovascular vulnerability

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