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.