Mineralocorticoid receptor blockade during a rat’s first violent encounter inhibits its subsequent propensity for violence.

Abstract

In individuals naïve to serious conflict in an unfamiliar environment, violence has long-lasting effects on subsequent aggressive behavior. This effect of the stressful experience of a first violent conflict occurs in victims as well as offenders. The authors study in the male rat as offender the role of a rapid corticosterone signal mediated by brain mineralocorticoid receptors (MR) in adjusting the threshold of aggressive responses. For this purpose, the authors have applied electrical stimulation of the brain's aggression circuit via the hypothalamic attack area or HAA. Using this paradigm, they found that in inexperienced rats, retesting of the animals on subsequent days facilitated aggression. Hypothalamic attack thresholds decreased to about 50% of their initial level. However, blocking the MR once with the mineralocorticoid antagonist spironolactone, during the very first evoked attacks, permanently prevented attack facilitation in subsequent conflicts in that same environment. The MR-mediated effect blocked by the antagonist occurred within an hour following the start of the first aggression tests only. A later MR blockade was not effective. These findings suggest that the corticosterone stress response during a very first serious conflict initializes an enhanced propensity for violent aggression through the brain MR.

Enhanced Emotional Empathy after Mineralocorticoid Receptor Stimulation in Women with Borderline Personality Disorder and Healthy Women

“…Interestingly, these impairing effects of MR blockade were most pronounced for emotional memory (Rimmele et al, 2013). This fits very well with animal data showing that MR are particularly involved in the appraisal of novel situations and in modulating stress-associated emotional reactions (Ter Horst et al, 2012;de Kloet, 2013;Kruk et al, 2013).…”

“…Therefore, it is plausible that MR influences emotional empathy given that emotional empathy, ie, the ability to share the emotional experience of another person, contributes importantly to appraisal processes and emotional reactions especially in stressful situations. Obviously, the degree of emotional empathy that a person is feeling (or not feeling) in a given situation modulates the appraisal of that situation and response strategies (Ter Horst et al, 2012;de Kloet, 2013;Kruk et al, 2013). However, at present, it remains unclear why MR stimulation improves emotional but not cognitive empathy and further studies need to replicate and further explore these findings (Zhou et al, 2011).…”

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The brain mineralocorticoid receptor: a saga in three episodes

“…These steroid effects mediated by MR proceed in a complementary fashion with GR-mediated actions. The effects of corticosteroids in the brain therefore depend on a fine-tuned balance between MR and GR that upon activation shifts energy resources to circuits and alter their connectivity underlying arousal, emotional expressions of fear and aggression, cognitive performance, motivation, reward and aversion (Korte et al 1995, Kruk et al 2013, Hermans et al 2014, Sousa 2016, Vogel et al 2016a. Thus, aldosterone not only evokes salt appetite but also reciprocally affects limbic-forebrain functions, via MR-based NTS and circumventricular networks , Evans et al 2016; the limbic-forebrain circuits themselves express abundantly MRs, which prefer corticosterone and cortisol.…”

Effects of mineralocorticoid receptor blockade on empathy in patients with major depressive disorder

“…Thus, the role of the MR in the context of empathy and other aspects of social cognition needs to be further investigated in different populations of health and disease. In any event, however, it seems to be plausible that MR influences empathy given that the MR has been associated with the appraisal of novel situations and related response strategies as well as with stress-associated emotional reactions (de Kloet, 2013;Kruk et al, 2013;Ter Horst et al, 2012,).…”