Osmoreceptor localization in the brain of the pigeon (Columba livia)

The area of the brain of pigeons that may be responsible for drinking following intravascular administration of osmotically effective solutes was investigated using infusions of water or isotonic and hypertonic solutions of NaCl or sucrose into various regions of the brains of conscious birds, and measuring the volume of water drunk. The preoptic area and the lateral hypothalamus were the only areas from which dose related drinking could be obtained in response to bilateral infusions of hypertoni NaCl or sucrose. Unilateral infusion of the hypertonic solutions rarely produced drinking. In contrast, water or isotonic NaCl, when infused unilaterally, in some cases caused some water intake. Drinking in response to intravenous infusion of hypertonic NaCl was not abolished by an ‘apparent’ lesion of the preoptic area. In several cases infusion of water or sucrose into the preoptic area caused a small volume of isotonic saline solution to be drunk. Thus the preoptic area and the lateral hypothalamus appear to be at least two of the areas involved in osmoregulation in the pigeon and may also be involved in sodium regulation.     

Osmotic activation of the hypothalamo-neurohypophysial system reversibly downregulates the NMDA receptor subunit, NR2B, in the supraoptic nucleus of the hypothalamus.

NMDA receptor activation produces a characteristic pattern of neuronal firing in magnocellular neuroendocrine cells (MNCs) of the supraoptic nucleus of the hypothalamus (SON) which has been associated with greater hormone release in vivo and in vitro. In addition, i.c.v. administered NMDA receptor blockers suppress the dehydration-induced rise in plasma vasopressin and drinking. To investigate the role of NMDA receptor subunits in the neuroendocrine functions of the magnocellular neuroendocrine cells of the hypothalamus, we examined the effects of osmotic stimulation on the protein expression of the NMDA receptor subunits, NR1 and NR2B, important in binding glycine and glutamate, respectively. Homogenates of SON, paraventricular nucleus of the hypothalamus (PVN), cortex and lateral hypothalamus from control rats and rats given 2% saline water to drink for 4-10 days were subjected to SDS-PAGE and Western blot analysis. This saline water drinking regimen produced a significant rise in plasma osmolality levels. NR1 and NR2B immunoreactivity was detected in SON, PVN, lateral hypothalamus and cortex but not in liver homogenates using subunit-specific polyclonal antibodies and quantified using computer-assisted densitometry. Mean NR2B immunoreactivity was significantly lower in SON (29%) and PVN homogenates (23%) from saline-treated rats than in those from control rats. In addition, the effect of dehydration on NR2B was regionally specific since no significant changes in NR2B expression were observed in homogenates of cortex and lateral hypothalamus. Rehydration allowed recovery of plasma osmolality as well as NR2B protein levels in the SON. These results suggest that changes in NMDA receptor subunit expression contribute to the plasticity manifested by in magnocellular neuroendocrine cells in response to osmotic activation of the hypothalamo-neurohypophysial system. In addition, our results indicate that NMDA receptors on SON and PVN MNCs may contribute to neuroendocrinological functions associated with body fluid homeostasis.     

Specific deficits in regulatory drinking following electrolytic lesions of the lateral hypothalamus

The possibility that cellular and extracellular thirst signals are transmitted by separate neural pathways in the lateral hypothalamus was investigated by administering peripheral and central thirst challenges and placing electrolytic lesions in two stages in the farlateral and midlateral hypothalamus. Lesions of the farlateral hypothalamus disrupted water intakes elicited by peripheral and central administration of NaCl (doses of 1.0, 2.0, and 4.0 osm) and sucrose (doses of 0.5, 1.0, 2.0 and 4.0 osm) without attenuating drinking to angiotensin II microinjected into the preoptic region (doses of 25, 50, 100, and 500 ng). Although the larger farlateral hypothalamus lesions, which destroyed the ventromedial part of the internal capsule, medial edge of the globus pallidus, and farlateral aspects of the lateral hypothalamus, caused motor impairments and some loss of body weight, these changes were minor and restricted to the immediate postlesion period. Smaller farlateral hypothalamus lesions, in which tissue damage was restricted to the farlateral hypothalamus and medial internal capsule, had little or no effect on rate of body weight gain or motor functions but were as effective as the larger lesions in disrupting water intake to NaCl and sucrose. Lesions of the midlateral hypothalamus attenuated water intake to angiotensin II given centrally without affecting drinking to centrally administered NaCl or sucrose. These observations indicate that the effects of far- and midlateral hypothalamic lesions are due to interruption of neural pathways mediating cellular and extracellular thirst signals, respectively, and not to nonspecific deficits.     

Intracerebroventricular dopamine attenuates sodium-induced but not angiotensin-induced drinking in minipigs

Drinking in response to dopamine (100 μg) injected into the lateral cerebral ventricles (i.c.v.), alone, or together with angiotensin II (AII, 300 ng) or hypertonic NaCl (1.4 Osm) was studied in water-replete minipigs trained to obtain their water under operant conditions. Dopamine itself was ineffective at producing drinking and it did not affect AII-induced drinking. Drinking in response to hypertonic NaCl was significantly attenuated by dopamine. Therefore in minipigs angiotensin-induced drinking does not appear to operate through a dopaminergic mechanism whereas sodium-induced drinking does.     

Modulation of salt appetite by lateral ventricular infusions of angiotensin II and carbachol during sodium depletion

Infusion of carbachol into the lateral ventricles of rats at rates of 400 or 2000 ng/h for 6 h produced dose-related natriuresis, kaliuresis, and water drinking but no consumption of hypertonic NaCl solution. Electrolyte excretion and water intake were maximal during the first 2 h, and no further increases occurred after 4 h. Sodium losses were estimated as 15–30% of total extracellular sodium. Continuous infusion of 2000 ng/h carbachol for 6 days produced a chronic increase of water intake but no increased consumption of saline. sodium balances were negative during the first day of infusion, but gradually returned to normal over 6 days. Plasma volume, hematocrit, and plasma sodium and potassium concentrations were normal in carbachol-infused animals on the 6th day. Cholinergic stimulation of the brain thus appeared to interfere with the usual salt appetite following sodium loss.     

Effects of SFO lesion or captopril on drinking induced by intragastric hypertonic saline

This study examined the hypothesis that the subfornical organ (SFO), a circumventricular organ with both osmosensitive elements and dipsogenic receptors for circulating angiotensin (ANG) II, is important for the water drinking response that follows an intragastric (ig) load of hypertonic NaCl. A 2-ml saline load was administered ig at 300, 900, or 1200 mOsm/kg to rats with sham lesions or lesions of the SFO, and intake was measured periodically for 2 h. Hypertonic loads caused sham-lesioned rats, but not SFO-lesioned rats, to drink earlier in the test or to drink more water than did the isotonic load. Inhibition of ANG II synthesis in unoperated rats with 100 mg/kg of captopril reduced water intake only during the initial 15 min after a gavage of 1200 mOsm/kg saline. Loads of 900 and 1200 mOsm/kg both increased plasma osmolality and sodium concentration by 15 min after gavage without greatly affecting hematocrit or plasma protein concentration. Thus, the SFO is important for the osmotically-induced water drinking response after acute ig administration of hypertonic saline. With the possible exception of the first 15 min, this drinking response is independent of the peripheral synthesis of ANG II.     

Lesions of the diagonal band of broca enhance drinking in the rat

This study examined the role of the diagonal band of Broca (DBB) in drinking behaviour and vasopressin release. Adult male rats were anaesthetized (pentobarbital 50 mg/kg) and received DBB injections of either ibotenic acid (0.5 microl of 5 micro g/ microl) or vehicle (0.5 microl of phosphate-buffered saline). Although baseline drinking and urine output were not affected, drinking to 30% polyethylene glycol (MW 8000; 1 ml/100 g s.c.) and angiotensin II (0, 1.5 and 3.0 mg/kg s.c.) were significantly increased in ibotenic acid in phosphate-buffered saline (DBBX) rats. Drinking to hypertonic saline (0.9, 4 and 6%; 1 ml/100 g), and water deprivation were not significantly affected. DBBX rats had significantly lower basal heart rates than controls but the cardiovascular responses to infusions of angiotensin II (100 ng/kg/min i.v. for 45 min) were not affected. DBBX rats had significantly higher basal vasopressin, but angiotensin-stimulated vasopressin release was not significantly different. Although the DBB is not involved in basal water intake, it is involved in dipsogenic responses to hypovolemic stimuli and possibly basal autonomic function and basal vasopressin release.     

Different brain structures mediate drinking and sleep suppression elicited by the somatostatin analog, octreotide, in rats

When injected into the cerebral ventricles, the somatostatin analog, octreotide (OCT) elicits prompt drinking, vasopressin secretion and increases in blood pressure that are attributed to the activation of the intracerebral angiotensinergic system. In addition, OCT induces sleep responses that might be mediated by an inhibition of hypothalamic neurons producing growth hormone-releasing hormone (GHRH). OCT (0.02 microg in 0.2 microl) was microinjected into various brain sites to determine the structures inducing drinking and/or sleep suppression in response to OCT in rats. Drinking (>1 ml water in 10 min) was elicited in 17 rats out of 86 tested. The positive drinking sites resided in or around the subfornical organ (SFO) and the paraventricular nucleus. Both structures are part of the reported angiotensinergic dipsogenic circuit of the brain. These microinjections failed to elicit consistent sleep effects. Sleep suppression (>10% recording time in hour 1) was observed after injection of OCT either into the arcuate nucleus (n=7), where the majority of GHRHergic neurons reside, or into the medial preoptic area/anterior hypothalamus (n=8), where GHRH acts to promote sleep. Administration of OCT into far lateral sites of the lateral preoptic area and lateral hypothalamus stimulated sleep in hour 1 (n=10), perhaps via inhibiting cholinergic neurons previously implicated in arousal. The results are consistent with the hypothesis that somatostatin is involved in the regulation of both water intake and sleep, and suggest that different structures, and therefore different somatostatinergic neuronal pools, mediate these actions.     

Pressor effect of centrally administered sodium chloride: role of the ventral third ventricle region and the area postrema.

To determine the site(s) responsible for the central cardiovascular effect of hypertonic saline, 0.2 ml of 1.5 M NaCl was administered to anesthetized dogs via three routes, a lateral ventricle, the third ventricle and the cisterna magna. Intracisternal administration of hypertonic NaCl produced much prompter pressor and tachycardic responses than did administration via the other two routes. Covering the ventral third ventricle region with a petroleum jelly plug had the effect of abolishing the pressor response to lateral ventricular hypertonic NaCl but did not modify the response to intracisternal hypertonic NaCl. By contrast, electrolytic lesion of the area postrema attenuated the rise in blood pressure produced by the intracisternal NaCl without affecting the response to lateral ventricular NaCl. These results indicate that at least two sites, the ventral third ventricle region in the hypothalamus and the area postrema in the lower brainstem, are responsible for the acute hypertension induced by an increase in NaCl concentration in the cerebrospinal fluid of the dog.