Richter and sodium appetite: From adrenalectomy to molecular biology

Abstract

Nearly three-quarters of a century ago, Curt Richter removed the adrenal glands from rats and noted that the animal's vitality was dependent on its increased consumption of sodium chloride. In doing so, Richter revealed an innate behavioral mechanism that serves to maintain the hydromineral balance of an animal faced with sodium deficit. This experiment and others like it, led to the development of a field of research devoted to the investigation of salt appetite. The following is a discussion of how Richter's initial observations gave birth to an evolving field that incorporates multiple approaches to examine the drive to consume sodium. KeywordsSalt appetite; Angiotensin; Aldosterone; Corticosterone; Richter The Discovery of Salt AppetiteAt the time that Richter began his career at Johns Hopkins University much of the research examining ingestive behavior focused on the responses of individual organs or closely coordinated systems. Richter's pioneering work initiated a fundamental paradigm shift that moved the focus to adaptations of the organism as a whole. Specifically, he was interested in changes in behavior that compensated for perturbations in the internal environment. His approach toward investigation of such behaviors was as thorough as it was fundamental. Richter manipulated diet, interfered with the nervous system, and removed or replaced glandular secretions in attempt to understand the nutritional, neural, and endocrine signals that contribute to behavior.Richter created disturbances in the nutritional or mineral content of the internal environment with dietary deficiency. Subsequently, "self selection" experiments were performed where choices of different minerals and nutrients were presented for consumption. More often than not, animals would consume minerals and nutrients in amounts that would alleviate their experimentally-induced deficiencies. One of the most striking behaviors that Richter observed was that of rats voluntarily ingesting salt when faced with sodium deficit. Sodium chloride was removed from the rats' food and they were given access to water and 3 % NaCl solution. The intake of the NaCl solution was approximately 1% of the total diet, which remarkably, is the

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

“…Some authors have postulated a role in salt appetite and volume regulation of local synthesis of aldosterone in the hypothalamus and circumventricular organs , but see a commentary by Funder (2005). The action exerted by aldosterone on salt appetite may occur in synergy with angiotensin II, as was observed in the salt-depleted animal model generated by furosemide administration (Sakai et al 1986, Krause & Sakai 2007.…”

“…After adrenalectomy, salt appetite rises, which is readily normalised by aldosterone replacement, but with higher doses of the mineralocorticoid, salt appetite increases again. Glucocorticoids increase salt appetite by inducing MR and by sustaining-through activation of the mesolimbic dopaminergic level, the motivation to ingest salt (Krause & Sakai 2007).…”

“…BNST neurons innervate the limbic brain and the nucleus accumbens underlying motivation and reward behaviours likely with the goal to still salt appetite. Pathways from the nucleus accumbens and paraventricular neurons subsequently signal salt satiation and then aversion (Geerling et al 2006, Krause & Sakai 2007). This neuronal network may explain why interventions in the frontal brain regions such as e.g.…”

The Perceptual Characteristics of Sodium Chloride to Sodium-Depleted Rats

“…In most of these experiments, sodium appetite was elicited prior to conditioning, rather than the reverse as in the present study. For example, Frumkin (1975) reported that adrenalectomized rats, which are in a chronic state of sodium hunger (Richter 1936(Richter , 1956Krause and Sakai 2007;Geerling and Loewy 2008), failed to form taste aversions to NaCl and concluded that sodium appetite either prevents aversive conditioning to the taste of sodium or prevents the expression of a learned aversion. In that study, however, rats had ample experience with NaCl prior to conditioning, which is known to decrease the strength of taste aversion (e.g., Kalat 1974).…”

Physiological state tunes mesolimbic signaling: Lessons from sodium appetite and inspiration from Randall R. Sakai

“…Dr. Randall R. Sakai dedicated a substantial portion of his career to understanding the hormonal signals that arise from negative sodium balance and how those signals interact with the central nervous system to drive sodium intake – a phenomenon known as sodium appetite. Randall, together with his student Eric Krause, drafted a beautiful review of sodium appetite as an homage to the revolutionary work of Curt Richter, who first described sodium appetite in 1936 [4,5]. Randall and his co-authors over the years have focused on the hormonal responses to sodium depletion and the integration of these signals by central circuits to generate compensatory physiological processes and behaviors.…”