The role of renin-angiotensin-aldosterone system in the depressive-like effects of a chronic and unresolved sodium appetite.

摘要

The current thesis investigated the effects of homeostatic disturbances and the behaviors engaged by those disturbances (e.g., sodium depletion and the ensuing sodium appetite) on depressive- and anxiety-like behaviors in rats, with a particular emphasis on hedonic behavior. In the first set of experiments (Chapter Two) it was found that a chronic unresolved sodium appetite reduced an animal's motivation to interact with other rewards [e.g., lateral hypothalamic self-stimulation (LHSS)], and that antagonists for the mineralocorticoid receptor (MR) prevented those deficits. Chapter 3 reports that DOCA treatment with concurrent high salt intake increases urinary excretion of the stress hormone corticosterone (CORT) and that DOCA treatment with high salt intake engages a neurotrophic response [i.e., increased expression of brain-derived neurotrophic factor (BDNF) protein] in the amygdala. These observations are consistent with previous results using chronic stress models of depression in animals. Experiments in Chapter 4 investigated anxiogenic and depressive-like effects of DOCA treatment and found that DOCA treatment without saline available elicits a reduction in intake of a palatable 2% sucrose solution and that DOCA treatment regardless of saline availability can promote anxiety-like behavior. Chapter 5 describes studies exploring the effects of continuous access to a rewarding stimulus (i.e., free access to a running wheel) on subsequent responding for LHSS reward. Long-term access (2 or 5 weeks) to an exercise wheel had essentially the opposite effect as a chronic unresolved sodium appetite---an increased responding for LHSS. Results are discussed in relation to the interaction of an unresolved sodium appetite and the renin-angiotensin-aldosterone system (RAAS) on the development of depressive symptoms, especially anhedonia.