The expression of sodium appetite in the rat is controlled by a multitude of hormonal mechanisms evoked when the animal is sodium depleted. Research has shown that it is not the sodium deficiency itself but rather the synergistic action of angiotensin and aldosterone, hormones that are released in response to the sodium depletion, which 1) generate the appetite for salt, and 2) have long-term effects that enhance subsequent salt intake. The proposed experiments examine the genomic and non-genomic effects of steroids on sodium intake and are based upon a foundation of past research examining the neurohormonal basis of sodium intake in the rat. This research proposal attempts to extend the current understanding of how and where these hormones act in the brain to elicit their specific behavioral effects by using A) site specific directed stimulation of brain parenchyma by steroids to: 1) identify those brain areas sensitive to adrenal steroids in eliciting sodium intake, and 2) to examine the mechanism by which the steroids act, i.e., either by classical genomic actions on the neurons that require hours of activation prior to eliciting a behavioral response or by acting at putative membrane receptors such that changes in behavior occur within minutes after steroid application; and B) by using current cell and molecular biological techniques in an in viva preparation to examine the effects of selective interference of endogenous steroid and peptide receptor production in brain. In addition to increasing our understanding of a classic instance of self-regulatory behavior, this research has health relevance. These results may provide rational therapies for patients in whom sodium intake complicates the management of hypertension and renal disease. With a better understanding of how endocrine mechanisms operate in eliciting sodium intake, chemical therapies that interfere with the actions of the/hormones can be directed at different levels of its production or mechanisms of action to reduce the craving for sodium.
| Evanson, N K; Herman, J P; Sakai, R R et al. (2010) Nongenomic actions of adrenal steroids in the central nervous system. J Neuroendocrinol 22:846-61 |
| Krause, Eric G; de Kloet, Annette D; Sakai, Randall R (2010) Post-ingestive signals and satiation of water and sodium intake of male rats. Physiol Behav 99:657-62 |
