Effects of interleukin-1 beta injections into the subfornical organ and median preoptic nucleus on sodium appetite, blood pressure and body temperature of sodium-depleted rats.

Interleukin-1ß (IL-1ß) appears to be the mediator of the reciprocal communication between the brain and the immune system. IL-1ß has been shown to modulate homeostatic functions including fever, feeding, drinking and cardiovascular control. The aim of the present study was to investigate the effects of IL-1ß injections directly into the subfornical organ (SFO) and the median preoptic nucleus (MnPO) on salt appetite, hedonic response, locomotion, body temperature and blood pressure in sodium-depleted rats. IL-1ß injections into the SFO and MnPO at the doses of 0.2, 0.4, 0.8 and 1.6ng/0.2µl promoted a dose-dependent inhibition of salt intake in sodium-depleted rats. Results of the "dessert" test and the "open field" test suggested that the inhibition of salt appetite is not due to any changes in the hedonic aspect of ingestive behavior or to changes in locomotor activity. As expected, IL-1ß injections into the SFO and MnPO promoted an increase in body temperature. However, the fever induced by IL-1ß injected into the SFO was slower than the increase in body temperature obtained following IL-1ß injection into the MnPO. Furthermore, IL-1ß at a dose of 1.6ng/0.2µl directly injected into the MnPO led to a significant increase in blood pressure, while injection of the same concentration of IL-1ß into the SFO caused no significant change in blood pressure or heart rate. The action of pro-inflammatory cytokines may interfere with the normal control of body temperature, blood pressure and fluid homeostasis, producing the adjustment required to cope with infection and inflammation. Further studies are required to clarify the mechanisms involved in fever, blood pressure increase and inhibition of sodium appetite induced by injections of IL-1ß into the SFO and MnPO in sodium-depleted rats.

Blockade of 5-Ht3 receptors in the septal area increases Fos expression in selected brain areas.

Serotonin is widely distributed throughout the brain and is involved in a multiplicity of visceral, cognitive and behavioral responses. It has been previously shown that injections of different doses of ondansetron, a 5-HT3 receptor antagonist, into the medial septum/vertical limb of the diagonal band complex (MS/vDB) induce a hypertensive response in rats. On the other hand, administration of m-CPBG, a 5-HT3 agonist, into the MS/vDB inhibits the increase of blood pressure during restraint stress. However, it is unclear which neuronal circuitry is involved in these responses. The present study investigated Fos immunoreactive nuclei (Fos-IR) in different brain areas following the blockade of 5-HT3 receptors located in the MS/vDB in sham and in sinoaortic denervated (SAD) rats. Ondansetron injection into the MS/vDB increases Fos-IR in different brain areas including the limbic system (central amygdala and ventral part of the bed nucleus of the stria terminalis), hypothalamus (medial parvocellular parts of the paraventricular nucleus, anterodorsal preoptic area, dorsomedial hypothalamic nucleus), mesencephalon (ventrolateral periaqueductal gray region) and rhombencephalon (lateral parabrachial nucleus) in sham rats. Barodenervation results in higher Fos expression at the parvocellular and magnocellular part of the paraventricular nucleus, the lateral parabrachial nucleus, the central nucleus of amygdala, the locus coeruleus, the medial part of the nucleus of the solitary tract, the rostral ventrolateral medulla and the caudal ventrolateral medulla following 5-HT3receptor blockade in the MS/vDB. Based on the present results and previous data showing a hypertensive response to ondansetron injected into the MS/vDB, it is reasonable to suggest that 5-HT3receptors in the MS/vDB exert an inhibitory drive that may oscillate as a functional regulatory part of the complex central neuronal network participating in the control of blood pressure.

Blockade of 5-HT3 receptors at septal area increase blood pressure in unanaesthetized rats.

In the present study the role of 5-HT(3) receptors located at the medial septum/vertical limb of the diagonal band complex (MS/vDB) in the control of blood pressure in unanaesthetized rats was investigated. Microinjections of ondansetron, a selective 5-HT(3) receptor antagonist, into this area caused a dose-dependent increase in blood pressure. This rise was attenuated by the blockade of alpha-adrenoceptors with i.v. prazosin and blunted by the prior microinjection of losartan, an AT1 antagonist, into this brain area. Microinjections of the 5-HT(3) agonist m-CPBG into this area failed to have any effect on blood pressure in non-stressed rats but significantly reduced the stress-induced hypertensive response. The reflex bradycardia evoked by i.v. phenylephrine was significantly increased after microinjections of ondansetron into this brain area but not the tachycardia evoked by i.v. sodium nitroprusside, suggesting that the pressor part of baroreflex has been enhanced. The data suggest that 5-HT(3) receptors at this brain level exert a tonic sympathoinhibitory action that is mediated via the local release of angiotensin in the MS/vDB. This tonic 5-HT(3) receptor drive also exerts an inhibitory action on the pressor component of the baroreflex. Also, the present data show that 5-HT(3) receptors located in the MS/vDB participate in the regulation of stress-induced hypertensive response.

Effects of acute heat exposure on prosencephalic c-Fos expression in normohydrated, water-deprived and salt-loaded rats.

In the present study, the distribution pattern of c-Fos protein immunoreactivity (Fos-IR) in prosencephalic areas of the brain involved in thermoregulatory and osmoregulatory responses was investigated, in rats exposed or not exposed to a hyperthermic environment, under three different conditions: normohydration, dehydration induced by water deprivation and hyperosmolarity induced by an acute intragastric salt load. Normohydrated, water-deprived or salt-loaded male Wistar rats (270+/-30 g) were submitted or not to acute heat exposure (33 degrees C for 45 min). A separate group of animals was submitted to the same experimental protocol and had blood samples collected before and after the heating period to measure serum osmolarity and sodium. The brains were processed for c-Fos immunohistochemistry using the avidin-biotin peroxidase method. After analyzing Fos-IR in the brains of animals in the present study, three different types of prosencephalic areas were identified: (1) those that respond to hydrational and to heat conditions, with an interaction between these two factors (PaMP and SON); (2) those that respond to hydrational and to heat conditions, but with no interaction between these factors (MnPO, LSV and OVLT); and (3) those that respond only to hydrational status (SFO and PaLM).

Involvement of central H1 and H2 receptors in water intake induced by hyperosmolarity, hypovolemia and central cholinergic stimulation.

In the present study we investigated the participation of central H1 and H2 histaminergic receptors in water intake induced by hyperosmolarity (evoked by intragastric salt load), by hypovolemia (promoted by the subcutaneous administration of polyethyleneglycol) and by the pharmacological stimulation of central cholinergic pathways by the muscarinic agonist carbachol in male Wistar rats. The data presented here show that the pharmacological blockade of central H1 histaminergic receptors by third ventricle injections of mepyramine significantly decreased water intake induced by hyperosmolarity, hypovolemia and by the intracerebroventricular injections of carbachol. On the other hand, the pharmacological blockade of central H2 histaminergic receptors by third ventricle injections of cimetidine significantly reduced water intake in hypovolemic and hyperosmotic animals, but failed to alter water intake induced by central cholinergic stimulation by carbachol. We conclude that H1 and H2 brain histaminergic receptors are involved in inducing thirst during hyperosmolarity and hypovolemia and that H1 histaminergic receptors located post-synaptically in relation to cholinergic pathways seem to be important in triggering drinking following central pharmacological cholinergic stimulation.

Corticotropin-releasing hormone in the lateral parabrachial nucleus inhibits sodium appetite in rats.

The present study investigated the role of corticotropin-releasing hormone (CRH) in the lateral parabrachial nucleus (LPBN) in the behavioral control of body fluid homeostasis by determining the effect of bilateral injections of the CRH receptor antagonist, alpha-helical corticotropin-releasing factor (CRF)(9-41), and the CRH receptor agonist, CRH, on sodium chloride (salt appetite) and water (thirst) intake. Groups of adult, male Sprague-Dawley rats had stainless-steel cannulas implanted bilaterally into the LPBN and were sodium depleted or water deprived. Bilateral injections of alpha-helical CRF(9-41) into the LPBN significantly potentiated water and salt intake in the sodium-depleted rats when access to fluids was restored. Bilateral injections of alpha-helical CRF(9-41) into the LPBN (1.0 microg) also increased sodium appetite in water-deprived rats. Conversely, in sodium-depleted animals, bilateral injections of CRH inhibited sodium chloride intake. These results suggest that there is an endogenous CRH inhibitory mechanism operating in the LPBN to modulate the intake of sodium (salt appetite). This mechanism may contribute to the behavioral control of restoration of body fluid homeostasis in sodium-deficient states.

Central H1 and H2 receptor participation in the control of water and salt intake in rats.

The aim of the present study was to evaluate the participation of brain H1 and H2 histaminergic receptors on water and salt intake induced by water deprivation (24 h), furosemide-induced sodium depletion and central angiotensinergic pharmacological stimulation in rats. Third ventricle injections of the H1 and H2 receptor antagonists, mepyramine (50, 100, 200 and 400 nmol) and cimetidine (100, 200 and 400 nmol), were unable to modify water intake induced by water deprivation and sodium depletion. Salt intake elicited by water deprivation and sodium depletion was reduced by the central administration of mepyramine, while intracerebroventricular administration of cimetidine had no effect. Water and salt intake evoked by central angiotensinergic stimulation (10 ng) was diminished by third ventricle injections of both mepyramine and cimetidine. Inhibition of the ingestive behaviors observed here is not a result of any illness-like effect produced by the intracerebroventricular injections of the histaminergic antagonists used, as demonstrated by an avoidance test. It was also shown that third ventricle injections of these compounds were unable to modify the hedonic behavior that leads rats to drink a tasty saccharin solution. We conclude that central histaminergic receptors participate in the control of salt intake induced by distinct physiological and pharmacological stimuli.

Histaminergic H1 and H2 receptors located within the ventromedial hypothalamus regulate food and water intake in rats.

The aim of the present study was to investigate the effect of the pharmacological blockade of histamine H1 and H2 receptors located within the ventromedial hypothalamus (VMH) on overnight food and water intake and on water intake elicited by two physiological stimuli: hyperosmolarity induced by an acute intragastric salt load and water deprivation. During the overnight period, the pharmacological blockade of both H1 and H2 VMH receptors significantly increased food intake and decreased water intake. In hyperosmotic rats, the blockade of H1 VMH receptors reduced water intake, while the blockade of H2 receptors in this same region yielded no significant effect. Additionally, in water-deprived rats, the blockade of both H1 and H2 receptors located within the VMH induced a significant decrease in water intake. The inhibitory effects on drinking behavior observed in this study do not seem to be a consequence of any "illness-inducing" effect provoked by the central administration of the antihistaminergic agents employed here, because an aversion test indicated that the injection of those compounds into the VMH does not induce any "illness-like" effect. In addition, the central administration of either mepyramine or cimetidine to dehydrated and hyperosmotic rats did not produce any reduction in locomotor activity measured in an open-field arena. Injections of the antihistaminergic agents used here into the regions that circumscribe the VMH produced no significant effects on water or food intake, indicating that the actions observed here may be specifically attributed to the set of histaminergic receptors situated within the VMH.