Abstract

Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions.

Highlights

  • The precise regulation of salt and water balance is essential for survival and good health, and when threatened, osmotic stability is aggressively defended

  • Salt intake in SD rats In two-bottle choice tests, rats showed a strong preference for isotonic saline (IS), ingesting significantly more compared with water (Fig. 1A)

  • The preference score for salt significantly decreased in rats presented with hypertonic saline (HS) compared to IS solutions in two-bottle choice tests (Fig. 1C)

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Summary

Introduction

The precise regulation of salt and water balance is essential for survival and good health, and when threatened, osmotic stability is aggressively defended. Integrated neuroendocrine and behavioural mechanisms function to control the excretion and consumption of water and salt in order to maintain the optimal bodily composition required for good health [1]. The neural organisation subserving the instinct of salt craving, which in evolutionary terms has a high survival value, appear to be plastic with respect to chronically high salt intake, resulting in enduring pathogenic changes in salt appetite and consumption [5]. The neuroendocrine reflexes regulating salt and water balance are centred on the hypothalamo-neurohypophyseal system (HNS). The rise in plasma osmolality that follows high salt ingestion is detected by intrinsic MCN mechanisms [6] and by specialised osmoreceptive neurons in the circumventricular organs such as the subfornical organ, which provide excitatory inputs to shape the firing activity of MCNs for hormone secretion [7] and parvocellular neurons for activation of the sympathetic nervous system [3]

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