-Salt loading (SL) and water deprivation (WD) are experimental challenges that are often used to study the osmotic circuitry of the brain. Central to this circuit is the supraoptic nucleus (SON) of the hypothalamus, which is responsible for the biosynthesis of the hormones, arginine vasopressin (AVP) and oxytocin (OXT), and their transport to terminals that reside in the posterior lobe of the pituitary. On osmotic challenge evoked by a change in blood volume or osmolality, the SON undergoes a functionrelated plasticity that creates an environment that allows for an appropriate hormone response. Here, we have described the impact of SL and WD compared with euhydrated (EU) controls in terms of drinking and eating behavior, body weight, and recorded physiological data including circulating hormone data and plasma and urine osmolality. We have also used microarrays to profile the transcriptome of the SON following SL and remined data from the SON that describes the transcriptome response to WD. From a list of 2,783 commonly regulated transcripts, we selected 20 genes for validation by qPCR. All of the 9 genes that have already been described as expressed or regulated in the SON by osmotic stimuli were confirmed in our models. Of the 11 novel genes, 5 were successfully validated while 6 were false discoveries. transcriptome; supraoptic nucleus; water restriction; salt load; neuroendocrine TERRESTRIAL LIFE requires that the osmolality of the extracellular fluid (ECF) is strictly controlled. Increased ECF osmolality results in water leaving the cell, reducing intracellular fluid (ICF) volume, while increasing ICF osmolality, which will compromise the metabolic processes necessary for life. Chronic increases in ECF osmolality can be brought about experimentally by a high intake of salt (salt loading, SL) or by water deprivation (WD) (5). In the absence of drinking fluid (WD), extracellular and intracellular fluid volumes decrease, as water and sodium are inevitably lost in sweat and urine leading to hypovolemia and, as a consequence of dehydration-induced natriuresis, sodium depletion (14,35). This depletion of sodium means that WD animals also display enhanced salt appetite (14). In contrast, SL increases body sodium content, causing an increase in ECF volume, but a decrease in the volume of the ICF (35).Angiotensin II (ANG II), atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and oxytocin (OXT) are the main hormones involved in the control of hydromineral homeostasis in mammals (5). ANP is synthesized and secreted into the bloodstream in response to stretching of the right atrial muscle cells by increased blood volume. Once in the bloodstream, ANP has a potent natriuretic effect, acting on the distal convoluted tubule of the nephron to inhibit sodium reabsorption (13,44). ANP is an important indicator of blood volume. AVP and OXT release are stimulated by hypovolemia, hypertonicity, and hypernatremia, among other stimuli (36). Circulating levels of AVP correlate with plasma osmolality (4) and thirst perce...