Neurochemical circuits implicated in sodium and fluid balance regulation

VIVAS, L.

RIBEIRAO PRETO SAN PABLO BRASIL

Simposio; Symposium of modern methodologies for the study of integrative physiology.; 2009

AMERICAN PHYSIOLOGICAL SOCIETY

Neurochemical circuits implicated in sodium and fluid balance regulation Vivas L., Instituto Ferreyra (INIMEC CONICET), Córdoba, Argentina.     The serotonergic dorsal raphe neurons (DRN) and their terminals within the lateral parabrachial nucleus (LPBN) are part of a key integrative neural network that receives and integrates signals derived from the electrolyte-fluid sensory system. Modulation of salt and water intake involves interactions between the Lamina Terminalis (LT) receptive areas and inhibitory hindbrain serotonergic circuits. That is, for normal thirst and sodium appetite sensations, and consequently appropriate water and salt drinking after electrolyte and fluid depletion, the released ANG II should act centrally both to activate brain angiotensinergic mechanisms that stimulate thirst and salt appetite, and also to inhibit brain serotonin (5-HT) mechanisms that inhibit thirst and sodium appetite, thus removing a “braking” mechanism. The central 5-HT circuits underlying this interaction mainly include bi-directional connections between the LT, 5-HT neurons of the DRN and 5-HT terminals within the LPBN. Our connectional, electrophysiological and c-fos expression studies reveal that the activity of serotonergic DRN change after body sodium status and fluid volume alterations. Regarding sodium appetite regulation our results are consistent with the concept that there is a tonic inhibition of sodium appetite exerted by serotonergic cells originating in the DRN. Such an inhibitory influence would be likely to be reduced in a state of fluid deficiency and increased when the animals ingest water and NaCl to restore hydromineral balance. On the other hand our recent physiological and connectional studies (Godino et al., 2007; Badaue et al., 2007) indicate that structures of the LT inform the DRN of sodium status during the satiety process of sodium appetite. In this way, cells within the LT may contribute to inhibitory mechanisms involving 5-HT neurons of the DRN, which limit the intake of sodium and prevent excess volume expansion. In addition, there is also evidence suggesting the existence of a serotonergic pathway with cell bodies in the raphé system and with terminals within the LPBN involved in the regulatory control of water/sodium intake and excretion (Petrov et al., 1992; Menani et al., 1996, 1998, 2000; Margatho et al., 2007, 2008). For example, it has been demonstrated that injection into the LPBN of methysergide, a nonselective 5-HT1/5-HT2 serotonergic receptor antagonist, increases the intake of water and NaCl induced by different central or systemic treatments and reduced the effects of blood volume expansion on increased Na+ and K+ excretion and urinary volume.  On the other hand, water intake induced by ANG II is significantly reduced after injection into the LPBN of either serotonin or the serotonergic 5-HT2a/5-HT2c receptor agonist (+/-)-2,5-dimetoxy-4-iodoamphetamine hydrochloride (DOI) which also enhanced the effects of blood volume expansion on Na+ and K+ excretion and urinary volume. Methysergide, into the LPBN also decreased the effects of blood volume expansion on plasma atrial natriuretic peptide (ANP) and oxytocin (OT), while DOI increased them. Taken together, these data provides further support to the idea that serotonergic terminals within the LPBN play an important regulatory role on induced water and sodium intake and blood volume expansion response. The presentation will also review our last electrophysiological data showing how the serotonergic system is specifically involved in the processing of osmotic signals in models of body sodium overload without changes in fluid volume.