Aldosterone Action on Brain and Behavior

Aldosterone's primary role is to maintain sodium homeostasis as regulated by the renin–angiotensin–aldosterone system. Besides angiotensin and ACTH, potassium is a major contributor for the release of aldosterone. It is also a stress hormone, which is triggered not only by ACTH (like cortisol/corticosterone), but is in addition stimulated via the sympathetic nervous system via beta-adrenergic pathways and the renin–angiotensin system. Activation of the mineralocorticoid receptor (MR) by aldosterone leads to an increase in blood pressure and sodium retention and has proinflammatory activity, thus preparing the organism for a fight or flight reaction. Further, social isolation, which is a risk factor for anxiety and depression, is related to an increase in aldosterone. A close interaction with oxytocin regulation appears to exist. Classical hippocampal MR are to a large degree occupied by cortisol/corticosterone most of the time and aldosterone has a limited effect. MRs in specific brain areas, primarily the nucleus of the solitary tract (NTS), are sensitive to aldosterone. Reciprocal connections exist between the NTS and behaviorally relevant areas, including the central nucleus of the amygdala, the paraventricular nucleus, the nucleus accumbens, the anterior cingulate cortex, and the insula. An aldosterone-sensitive functional system emerges, which is involved in the control of vegetative regulation, like that of blood pressure, heart rate, slow wave sleep, salt appetite, but also interoception and emotionality. This system is modified by both genetic and epigenetic levels. MR activity-related biomarkers can be utilized to further characterize specific groups of patients, which are treatment refractory to standard antidepressants and who may require a manipulation of the MR activity in order to show clinical improvement.