Abstract
Stress-related neuropsychiatric (e.g., anxiety, depression) and cardiovascular diseases are frequently comorbid, though discerning the directionality of their association has been challenging. One of the most controllable risk factors for cardiovascular disease is salt intake. Though high salt intake is implicated in neuropsychiatric diseases, its direct neurobehavioral effects have seldom been explored. We reported that elevated salt intake in mice augments neuroinflammation, particularly after an acute stressor. Here, we explored how high salt consumption affected behavioral responses of mice to mildly arousing environmental and social tests, then assessed levels of the stress-related hormone corticosterone. Unexpectedly, anxiety-related behaviors in the elevated plus maze, open field, and marble burying test were unaffected by increased salt intake. However, nest building was diminished in mice consuming high salt, and voluntary social interaction was elevated, suggesting reduced engagement in ethologically-relevant behaviors that promote survival by attenuating threat exposure. Moreover, we observed significant positive correlations between social preference and subsequent corticosterone only in mice consuming increased salt, as well as negative correlations between open arm exploration in the elevated plus maze and corticosterone selectively in mice in the highest salt condition. Thus, heightened salt consumption reduces behavioral inhibition under relatively low-threat conditions, and enhances circulating corticosterone proportional to specific behavioral shifts. Considering the adverse health consequences of high salt intake, combined with evidence that increased salt consumption impairs inhibition of context-inappropriate behaviors, we suggest that prolonged high salt intake likely promulgates maladaptive behavioral and cardiovascular responses to perceived stressors that may explain some of the prevalent comorbidity between cardiovascular and neuropsychiatric diseases.
Highlights
Cardiovascular disease is closely associated with multiple neuropsychiatric diseases including post-traumatic stress disorder, depression, and anxiety (Player and Peterson, 2011; Cohen et al, 2015; Seldenrijk et al, 2015; Tully et al, 2016; Edmondson and Känel, 2017)
Our observation that increased salt intake did not significantly affect anxiety-related behaviors, while contrary to our hypothesis, is intriguing given the pronounced reductions in compulsive nest building and enhanced social interaction exhibited by mice consuming the 4% salt solution
These lowered behavioral inhibitions, in a mildly arousing social situation, may be indicative of an active coping response evoked by high salt intake, as we have previously observed in response to a highly arousing swim stress (Mitchell et al, 2018; Gilman et al, 2019a)
Summary
Cardiovascular disease is closely associated with multiple neuropsychiatric diseases including post-traumatic stress disorder, depression, and anxiety (Player and Peterson, 2011; Cohen et al, 2015; Seldenrijk et al, 2015; Tully et al, 2016; Edmondson and Känel, 2017). The combination of psychosocial stress – a key contributor to depressive and anxiety disorders – with increased salt intake has been recognized in humans as a potent precipitator of potentiated blood pressure, in salt-sensitive individuals (Henry, 1988; Staessen et al, 1994; Deter et al, 1997, 2001). Such stress-salt interactions are suspected to contribute to the close association between stress-related neuropsychiatric diseases and cardiovascular disease (Mitchell et al, 2018; Gilman et al, 2019a)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
