Fluid transitions.

Water is critical for survival and thirst is a powerful way of ensuring that fluid levels remain in balance. Overconsumption, however, can have deleterious effects, therefore optimization requires a need to balance the drive for water with the satiation of that water drive. This review will highlight our current understanding of how thirst is both generated and quenched, with particular focus on the roles of angiotensin II, glucagon like-peptide 1, and estradiol in turning on and off the thirst drive.

The estrogenic reduction in water intake stimulated by dehydration involves estrogen receptor alpha and a potential role for GLP-1.

It is well documented that estrogens inhibit fluid intake. Most of this research, however, has focused on fluid intake in response to dipsogenic hormone and/or drug treatments in euhydrated rats. Additional research is needed to fully characterize the fluid intake effects of estradiol in response to true hypovolemia.

Limited effects of dehydration on object discrimination in the novel object recognition paradigm in young and middle-aged male and female rats.

Dehydration is associated with impaired cognitive function in humans. Limited animal research also suggests that disruptions in fluid homeostasis impair performance in cognitive tasks. We previously demonstrated that extracellular dehydration impaired performance in the novel object recognition memory test in a sex and gonadal hormone specific manner.

Sex Differences in Salt Appetite: Perspectives from Animal Models and Human Studies.

Salt ingestion by animals and humans has been noted from prehistory. The search for salt is largely driven by a physiological need for sodium. There is a large body of literature on sodium intake in laboratory rats, but the vast majority of this work has used male rats.

The anti-dipsogenic and anti-natriorexigenic effects of estradiol, but not the anti-pressor effect, are lost in aged female rats.

Estradiol (E2) inhibits fluid intake in several species, which may help to defend fluid homeostasis by preventing excessive extracellular fluid volume. Although this phenomenon is well established using the rat model, it has only been studied directly in young adults. Because aging influences the neuronal sensitivity to E2 and the fluid intake effects of E2 are mediated in the brain, we tested the hypothesis that aging influences the fluid intake effects of E2 in female rats.

Bidirectional effects of estradiol on the control of water intake in female rats.

The inhibitory effect of estradiol (E2) on water intake has been recognized for 50 years. Despite a rich literature describing this phenomenon, we report here a previously unidentified dipsogenic effect of E2 during states of low fluid intake. Our initial goal was to test the hypothesis that the anti-dipsogenic effect of E2 on unstimulated water intake is independent of its anorexigenic effect in female rats.

Gonadal hormones in female rats protect against dehydration-induced memory impairments in the novel object recognition paradigm.

Dehydration impairs cognitive performance in humans and rodents, although studies in animal models are limited. Estrogens have both protective effects on fluid regulation and improve performance in certain cognitive tasks. We, therefore, tested whether sex and gonadal hormones influence object recognition memory during dehydration.

Novel high molecular weight albumin-conjugated angiotensin II activates β-arrestin and G-protein pathways.

Purpose: To study the ability of a novel bovine serum albumin-angiotensin II (BSA-Ang II) conjugate to effect responses of the AT angiotensin II receptor subtype mediated by the G-protein-coupled and the beta-arrestin pathways.

Methods: Angiotensin II (Ang II) was conjugated with bovine serum albumin and compared with Ang II for competition binding to AT receptors, to stimulate aldosterone release from adrenocortical cells, to promote beta-arrestin binding to AT receptors, to promote calcium mobilization, and stimulate drinking of water and saline by rats.

Results: The BSA-Ang II conjugate was less potent competing for ATR binding, but was equally efficacious at stimulating aldosterone release from H295R adrenocortical cells.

Sex Differences in the Behavioral Desensitization of Water Intake Observed After Repeated Central Injections of Angiotensin II.

Previous in vivo and in vitro studies demonstrate that the angiotensin type 1 receptor rapidly desensitizes after exposure to angiotensin II (AngII). Behaviorally, this likely underlies the reduced drinking observed after acute repeated central injections of AngII. To date, this phenomenon has been studied exclusively in male subjects.

Sex differences in angiotensin II-stimulated fluid intake.

What is the topic of this review? This report describes sex differences in the responses to angiotensin II, with a focus on fluid intake. What advances does it highlight? There are conflicting reports on the direction of the sex difference in fluid intake in response to angiotensin II. This review highlights how accounting for differences in body weight contributes to the discrepancies in the literature.

Associative learning contributes to the increased water intake observed after daily injections of angiotensin II.

Daily injections of angiotensin II (AngII) cause a progressive increase of water intake that resembles a classically ascribed non-associative sensitization. Consistent with the presumption that the observed increase in intake was sensitization, we hypothesized that it resulted from a pharmacological interaction between AngII and its receptor. To test this hypothesis, and remove the influence of drinking itself, we implemented a delay in water access after injection of AngII (icv) on four consecutive 'induction days,' and then measured intake on the next day ('test day') when rats were allowed to drink immediately after AngII.

Sex differences in the drinking response to angiotensin II (AngII): Effect of body weight.

Sex differences in fluid intake stimulated by angiotensin II (AngII) have been reported, but the direction of the differences is inconsistent. To resolve these discrepancies, we measured water intake by male and female rats given AngII. Males drank more than females, but when intake was normalized to body weight, the sex difference was reversed.

Divergent effects of ERα and ERβ on fluid intake by female rats are not dependent on concomitant changes in AT1R expression or body weight.

Estradiol (E2) decreases both water and saline intakes by female rats. The ERα and ERβ subtypes are expressed in areas of the brain that control fluid intake; however, the role that these receptors play in E2's antidipsogenic and antinatriorexigenic effects have not been examined. Accordingly, we tested the hypothesis that activation of ERα and ERβ decreases water and saline intakes by female rats.

Activation of G protein-coupled estrogen receptor 1 (GPER-1) decreases fluid intake in female rats.

Estradiol (E2) decreases fluid intake in the female rat and recent studies from our lab demonstrate that the effect is at least in part mediated by membrane-associated estrogen receptors. Because multiple estrogen receptor subtypes can localize to the cell membrane, it is unclear which receptor(s) is generating the anti-dipsogenic effect of E2. The G protein-coupled estrogen receptor 1 (GPER-1) is a particularly interesting possibility because it has been shown to regulate blood pressure; many drinking-regulatory systems play overlapping roles in the control of blood pressure.

Multiple estrogen receptor subtypes influence ingestive behavior in female rodents.

Postmenopausal women are at an increased risk of obesity and cardiovascular-related diseases. This is attributable, at least in part, to loss of the ovarian hormone estradiol, which inhibits food and fluid intake in humans and laboratory animal models. Although the hypophagic and anti-dipsogenic effects of estradiol have been well documented for decades, the precise mechanisms underlying these effects are not fully understood.

Roux-en-Y gastric bypass does not affect daily water intake or the drinking response to dipsogenic stimuli in rats.

Bariatric surgery is currently the most effective treatment for severe obesity, and Roux-en-Y gastric bypass (RYGB) is the most common approach in the United States and worldwide. Many studies have documented the changes in body weight, food intake, and glycemic control associated with the procedure. Although dehydration is commonly listed as a postoperative complication, little focus has been directed to testing the response to dipsogenic treatments after RYGB.

Amelioration of binge eating by nucleus accumbens shell deep brain stimulation in mice involves D2 receptor modulation.

Hedonic overconsumption contributing to obesity involves altered activation within the mesolimbic dopamine system. Dysregulation of dopamine signaling in the nucleus accumbens shell (NAS) has been implicated in reward-seeking behaviors, such as binge eating, which contributes to treatment resistance in obesity (Wise, 2012). Direct modulation of the NAS with deep brain stimulation (DBS), a surgical procedure currently under investigation in humans for the treatment of major depression, obsessive-compulsive disorder, and addiction, may also be effective in ameliorating binge eating.

Activation of membrane-associated estrogen receptors decreases food and water intake in ovariectomized rats.

Estradiol (E2) decreases food and water intake in a variety of species, including rats. Available evidence suggests that this is mediated by genomic mechanisms that are most often attributed to nuclear estrogen receptors. More recent studies indicate that membrane-associated estrogen receptors (mERs) also can influence gene expression through the activation of transcription factors, yet it is unclear whether mERs are involved in mediating the hypophagic and antidipsetic effects of E2.