Javier Mahía

Lesions of tuberomammillary nuclei induce differential polydipsic and hyperphagic effects

This study aimed to examine the function of the tuberomammillary complex in water and food intake of Wistar rats. The results show that lesions restricted to tuberomammillary subnuclei: caudal ventral tuberomammillary nucleus (E1), rostral ventral tuberomammillary nucleus (E2), medial ventral tuberomammillary nucleus (E3) or medial dorsal tuberomammillary nucleus (E4), induce a strong and persistent polydipsia with specific characteristics for each nucleus. Interestingly, the distribution of tuberomammillary hyperdipsia throughout the day was similar to that in non‐lesioned animals, in contrast to the lack of rhythmicity observed in rats with anodic lesion to median eminence. This polydipsia appears to be independent of food intake, as food deprivation for 22 h did not significantly reduce the water intake. Finally, lesions in ventral tuberomammillary nuclei E1 and E2 induce hyperphagia, confirming a possible role for the tuberomammillary complex in food intake. This increase in food intake is not observed after lesions in medial subnuclei E3 and E4. These results are interpreted in terms of the hypothalamic systems involved in the consumption of both food and water.

Dipsogenic potentiation by sodium chloride but not by sucrose or polyethylene glycol in tuberomammillary-mediated polydipsia

The aim of this study was to examine the dipsogenic mechanisms involved in the recently discovered tuberomammillary (TM)-mediated polydipsia. Rats with bilateral electrolytic lesions of each TM subnucleus underwent several dipsogenic treatments, both osmotic and volemic. Animals with ventral (E2) or medial TM lesions (E3 or E4) showed a potentiated hyperdipsic response to hypertonic sodium chloride administration but not to sucrose or polyethylene glycol treatments. The increase in response to sodium chloride was significantly greater in groups E3/E4 and E2 than in the non-lesioned group and in animals with polydipsia induced by lesion of the median eminence. As previously reported, hyperphagia was induced by lesion to ventral TM nuclei (E1 or E2), confirming a possible role for the TM complex in food intake. However, lesions in medial nuclei (E3 or E4) did not produce this increase in food intake. These results are interpreted in relation to the hypothalamic systems involved in food and water intake.

Animal models of Central Diabetes Insipidus: Human relevance of acquired beyond hereditary syndromes and the role of oxytocin

The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion. Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits.

Oxytocin Polyuria and Polydipsia is Blocked by NaCl Administration in Food‐Deprived Male Rats

We examined the effects of NaCl injections on the polydipsia and polyuria induced by subcutaneous oxytocin (OT) administration in food‐deprived male rats. During the first 12 h of the treatment day, both food deprivation and OT administration increased urine excretion but reduced water intake, water balance (fluid intake minus urine volume) and body weight. OT treatment enhanced urine excretion and the reduction in water balance and body weight without reducing the water intake of food‐deprived animals. Analysis of the physiological effects of OT administration showed increases in urinary sodium concentration, sodium excretion and a reduced plasma sodium concentration. During the second 12 h, OT increased both urine excretion and water intake in food‐deprived but not in ad lib.‐fed rats. However, hypertonic NaCl administration at the start of this second 12‐h period blocked the polyuric and polydipsic responses observed in the OT/deprived group but increased the water intake of the ad lib. groups. After the whole 24‐h period, animals treated with OT showed a water balance and body weight change matching those observed in Control animals. Although the recording time period is a critical factor to demonstrate the effect of peripheral OT administration on water intake, the results obtained suggest that the polyuric and polydipsic responses observed in food‐deprived animals depend on the negative sodium and water balance induced by the natriuretic effect of OT and the unavailability of sodium. These OT‐induced deficits can be counteracted by the administration of hypertonic NaCl solutions or simply by the intake of standard food.

The natriuretic effect of oxytocin blocks medial tuberomammillary polydipsia and polyuria in male rats

Lesions of the tuberomammillary complex, a neuroanatomical system closely related to the hypothalamic supraoptic and paraventricular nuclei, induce strong polydipsia in male rats. It was recently demonstrated that this increase in water intake is immediate, persistent, follows circadian rhythms and appears to be related to sodium regulation. The present study found that urine osmolality was significantly lower in tuberomammillary‐lesioned animals vs. their respective controls at 8:00 h after surgery. Therefore, the aim of the present study was to examine the natriuretic effect of intraperitoneal oxytocin (OT) administration on medial ventral tuberomammillary nucleus (E3) polydipsia and polyuria of lesioned and control male rats. At 24:00 h post‐lesion, OT blocked the hyperdipsic and polyuric responses of E3‐lesioned animals but not those of non‐lesioned controls, which did however significantly increase their water intake. Moreover, urinary osmolality and sodium excretion increased in E3 ‐lesioned animals that received OT but not in lesioned controls receiving physiological saline (992 ± 187.19 vs. 215.83 ± 23.39 mOsm/kg; 1.68 ± 0.13 vs. 0.47 ± 0.1 mEq/L). At 48:00 h post‐lesion, OT administration also induced a higher intake of water and of simultaneously offered hypertonic NaCl (1.5%) in E3‐lesioned animals. These results are interpreted in terms of the hypothalamic systems involved in sodium and water homeostasis.

NaCl preference and water intake effects of food availability in median eminence polydipsia

Lesions in the median eminence (ME) produce a well-known neurological model of polydipsia and polyuria in rats. The effect of food availability (ad lib/deprivation) on the polydipsic/polyuric behaviour of animals was tested. As expected, all lesioned rats developed strong polyuria and polydipsia during the first postoperative 24h. This effect was maintained during day 2 when food was available ad lib (experiment A), but both polyuria and polydipsia were abolished when animals were deprived of food during the next 24h (day 3). Animals deprived of food from the first post-operative day (experiment B) showed a significant reduction in the initial polyuria and polydipsia (day 1) on day 2, but these effects were again observed on day 3 when food was available ad lib. Finally, when food-deprived animals were able to choose between a 1.5% sodium chloride solution and water (experiment C), they preferentially chose (82% of total liquid consumed) the hypertonic saline solution (day 1); during the next 24h (day 2), when only water was available, the polyuric/polydipsic effect was abolished but returned when food became available ad lib on day 3. Hence, the polyuria/polydipsia effect produced by ME lesions appears to be consistent during the first 24h but might later be related to the availability of standard food and is completely abolished under food deprivation conditions. Preference for the hypertonic solution supports the volemic component of this syndrome and demonstrates the need for appropriate amounts of hypertonic nutrients to be consumed during the first 24h.

Hyperphagia and increased body weight induced by lesions of the ventral tuberomammillary system

Individual lesions of the caudal (E1) or rostral (E2) ventral tuberomammillary nuclei induced hyperphagia in Wistar rats. The aim of the present study was to examine the additive or united effects of combined lesions of E1+E2 in food intake. E1+E2 lesions produced an immediate, potent and permanent hyperphagic response that was greater than that observed in groups with individual lesions (E1 or E2) during the 22-day observation period. Furthermore, at the end of this period (Days 17/22), the combined lesions induced a greater increase in body weight compared with groups with individual lesions. As previously reported, polydipsia is also induced by lesions of the ventral tuberomammillary subnuclei. However, in this case, responses of the individual polydipsic groups did not differ from those found in the E1+E2 ventral tuberomammillary group. These results are interpreted in terms of the hypothalamic systems involved in food and water intake.

Differential lasting inhibitory effects of oxytocin and food-deprivation on mediobasal hypothalamic polydipsia.

This study analyzed the effects of systemic oxytocin (OT) administration and 48-h food deprivation on the polydipsia, hyperphagia, and polyuria produced by electrolytic lesions of the mediobasal hypothalamus (MBH). In a first experiment, food deprivation transiently decreased the polydipsic response, whereas food deprivation plus OT administration reduced the water intake and urine excretion of polydipsic animals but not their subsequent food intake. These results were replicated in a second experiment (20 days), which also showed that OT potentiates sodium excretion, reducing the estimated plasma sodium levels in food-deprived MBH-lesioned animals. Administration of OT on day 21 to food-deprived (from day 20 to 22) animals (second period of the experiment 2) blocked the differences in water intake and urine excretion volumes between MBH and control animals on days 21 and 22. Subsequently, this 48-h food deprivation induced an additional and lasting (days 23-40) reduction in the intake of water and food of MBH animals. According to these findings, OT administration and/or food deprivation may potentially exert enduring reducing effects on the polydipsia, polyuria, and hyperphagia of MBH syndrome.

Nucleus of the solitary tract and flavor aversion learning: relevance in concurrent but not sequential behavioral test.

Theories relating the nucleus of the solitary tract to taste aversion learning (TAL) have received their main support from immunohistochemical research. In the present study, a behavioral analysis was performed on the effect of lesions of the intermediate nucleus of the solitary tract (iNST) on concurrent and sequential flavor aversion learning tasks. Bilateral lesions of the iNST impaired concurrent flavor learning, in which animals must discriminate between two simultaneously presented flavors paired with intragastric administration of a noxious or innocuous substance, respectively. However, the same iNST lesions did not interrupt the development of sequential flavor aversion learning, in which each flavor is offered individually on consecutive alternate days. These results behaviorally confirm the relevance of the nucleus of the solitary tract in TAL and suggest a functional dissociation between the neural systems underlying concurrent and sequential flavor aversion learning.

Potentiated effect of systemic administration of oxytocin on hypertonic NaCl intake in food-deprived male rats.

Subcutaneous administration of oxytocin (OT) increases water intake and sodium/urine excretion in food-deprived male rats. This study analyzes the effect of OT administration (at 0830 and 1430h) on the consumption of water and hypertonic NaCl (1.5%). In the first experiment, injections of OT increased the intake of hypertonic NaCl (but not of water) in food-deprived rats but not in ad lib-fed animals during the second 12 h (2030 to 0830) of the treatment day. The net concentration of the fluid consumed by OT/deprived animals was close to isotonic. In the second experiment, the initial effect of OT administration was an increase in urine volume and urinary sodium excretion and concentration by food-deprived animals during the first 12 h (0830 to 2030). These findings suggest that in food-deprived animals, systemic administration of OT induces NaCl intake as a consequence of previous urine loss and urinary sodium excretion.