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.

Role of 5-HT3 and 5-HT2C receptors located within the medial amygdala in the control of salt intake in sodium-depleted rats.

In the present study, we investigated the role of 5-HT(3) and 5-HT(2C) receptors located within the medial amygdala (MeA) in the control of water and salt intake in sodium-depleted rats. Pharmacological activation of 5-HT(3) receptors located in the medial amygdala by the selective 5-HT(3) receptor agonist m-CPBG significantly reduced salt intake in sodium-depleted rats, an effect that is reverted by pretreatment with the selective 5-HT(3) receptor antagonist ondansetron. In addition, the injection of ondansetron alone into the medial amygdala had no effect on salt intake in sodium-depleted and in sodium-repleted rats. Pharmacological stimulation of 5-HT(2C) receptors located in the medial amygdala by the selective 5-HT(2C) receptor agonist m-CPP failed to modify salt intake in sodium-depleted rats, whereas the blockade of these receptors by the selective 5-HT(2C) receptor antagonist SDZ SER 082 significantly reduced salt intake in this same group of animals. These results lead to the conclusion that the pharmacological activation of 5-HT(3) receptors located within the MeA inhibits salt intake in sodium-depleted rats and that, in this same brain region, the functional integrity of 5-HT(2C) receptors is required to achieve the full expression of sodium appetite in sodium-depleted rats.

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.

Role of central 5-HT3 receptors in the control of blood pressure in stressed and non-stressed rats.

The aim of the present study was to investigate the participation of central 5-HT(3) receptors in the control of blood pressure and heart rate (HR) of non-stressed and stressed rats. The pharmacological stimulation of brain 5-HT(3) receptors by third ventricle injections of the selective 5-HT(3) receptor agonist m-CPBG induced a significant decrease in blood pressure in non-stressed rats and impaired the hypertensive response induced by restraint stress. The blockade of brain 5-HT(3) receptors by the central administration of the selective 5-HT(3) antagonist ondansetron elicited a significant increase in blood pressure in non-stressed rats. Conversely, the hypertensive response induced by restraint stress was not affected by central administration of ondansetron. Additionally, baroreflex-mediated bradycardia during phenylephrine-induced hypertensive response was preserved in non-stressed animals receiving third ventricle injections of m-CPBG, while the baroreflex-mediated tachycardia that occurs during the hypotensive response induced by the administration of sodium nitroprusside was impaired. It is concluded that the serotoninergic component represented by the brain 5-HT(3) receptors exerts a tonic inhibitory influence on the central control of blood pressure in non-stressed rats, probably by a sympathoinhibitory-related mechanism. On the other hand, during stress, this central 5-HT(3)-dependent inhibitory drive is overwhelmed by the different neurochemical systems that harmonically trigger and sustain the hypertensive response.

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.

Central 5-HT2B/2C and 5-HT3 receptor stimulation decreases salt intake in sodium-depleted rats.

In the present study, we investigated the participation of central 5-HT(2B/2C) and 5-HT(3) receptors in the salt intake induced by sodium depletion in Wistar male rats. Sodium depletion was produced by the administration of furosemide associated with a low salt diet. Third ventricle injections of mCPP, a 5-HT(2B/2C) agonist, at doses of 80, 160 and 240 nmol, promoted a dose-dependent reduction in salt intake in sodium-depleted rats. The inhibitory effect produced by central administration of mCPP was abolished by the central pretreatment with SDZ SER 082, a 5-HT(2B/2C) antagonist. Similar results were obtained with third ventricle injections of m-CPBG (80, 160 and 240 nmol), a selective 5-HT(3) agonist that also induced a dose-related decrease in salt intake in sodium-depleted rats. The central pretreatment with LY-278,584, a selective 5-HT(3) receptor antagonist, was able to impair the salt intake inhibition elicited by third ventricle injections of m-CPBG. Central administration of each one of the antagonists alone or a combination of both antagonists together did not significantly change salt intake after sodium depletion. On the other hand, the central administration of both mCPP and m-CPBG, in the highest dose used to test their effect on salt intake (240 nmol), was unable to modify blood pressure in sodium-depleted rats. It is concluded that: (1) pharmacological activation of central 5-HT(2B/2C) and 5-HT(3) receptors diminishes salt intake during sodium depletion, (2) an inhibitory endogenous drive exerted by central 5-HT(2B/2C) and 5-HT(3) receptors does not seem to exist and (3) the reduction in salt intake generated by the pharmacological activation of these central receptors is not produced by an acute hypertensive response.

Central 5-HT(3) receptors and water intake in rats.

In the present paper, we studied in rats the effect of third ventricle administration of m-chlorophenylbiguanide hydrochloride (1-(3-chlorophenyl)biguanide (m-CPBG), a selective 5-HT(3) agonist, on water intake induced by three different physiological stimuli: water deprivation, acute salt load and hypovolemia. Central acute m-CPBG injections in the doses of 80 and 160 nmol significantly reduced water intake elicited by an acute salt load. Third ventricle injections of m-CPBG in the dose of 160 nmol significantly inhibited water intake in hypovolemic animals, whereas third ventricle injections of m-CPBG in a higher dose (320 nmol) were necessary to decrease water intake in water-deprived rats. Pretreatment with 1-methyl-N-[8-methyl-8-azabicyclo(3.2.1)-oct-3-yl]-1H-indazole-3-carboxamide (LY-278,584), a selective 5-HT(3) antagonist, abolished the inhibitory effect on water intake seen after central administration of m-CPBG in all groups studied. The central administration of m-CPBG was also able to inhibit water intake induced by pharmacological activation of central cholinergic and angiotensinergic pathways. Third ventricle injections of m-CPBG in the highest dose employed in this study (320 nmol) were unable to modify food intake in food-deprived rats. An aversion test has shown that acute third ventricle injections of m-CPBG do not induce illness-like effects that could explain the water intake inhibition here observed. Also, central administration of m-CPBG did not modify the intake of a "dessert" meal consisting of diluted condensed milk. It is concluded that central 5-HT(3) receptor activation exerts a specific inhibitory effect on water intake.

Central administration of zinc reduces salt intake in rats.

The aim of the present study was to investigate the effect of third ventricle injections of zinc on salt intake in rats in the three different experimental models where sodium appetite is increased: fluid deprivation, central angiotensinergic stimulation and sodium depletion. Adult Wistar male rats received third ventricle injections of Zn(Ac)2 in three different doses (0.03, 0.3 and 3.0 nmol/rat). Central angiotensinergic stimulation was achieved by third ventricle injections of angiotensin II in the dose of 25 ng/rat 30 min before central zinc administration. As expected, fluid deprivation, central angiotensinergic stimulation and sodium depletion significantly increased sodium appetite. Water intake was also enhanced after fluid deprivation and central angiotensinergic stimulation. After sodium depletion, no increase in water intake was observed. Third ventricle injections of zinc inhibited salt intake in all three experimental models studied. Water intake was also inhibited by central zinc administration after fluid deprivation and central angiotensinergic stimulation. Conversely, third ventricle injections of zinc were unable to modify food intake or body temperature. It is suggested that zinc, acting on central structures related to the control of body fluid homeostasis, inhibits the drive for salt intake that is normally observed during fluid deprivation, central angiotensinergic stimulation and sodium depletion.