Abstract
In order to determine whether serotonergic (5HT) dorsal raphe nucleus (DRN) cells are involved in body sodium status regulation, the effect of a s.c. infusion of either 2 M or 0.15 M NaCl on 5HT DRN neuron firing was studied using single unit extracellular recordings. In separate groups of 2 M and 0.15 M NaCl-infused rats, water intake, oxytocin (OT) plasma concentration, urine and plasma sodium and protein concentrations were also measured. Also, to determine the involvement of particular brain nuclei and neurochemical systems in body sodium overload (SO), animals from both groups were perfused for brain immunohistochemical detection of Fos, Fos-OT and Fos-5HT expression. SO produced a significant increase in serotonergic DRN neuron firing rate compared to baseline and 0.15 M NaCl-infused rats. As expected, 2 M NaCl s.c. infusion also induced a significant increase of water intake, diuresis and natriuresis, plasma sodium concentration and osmolality, even though plasma volume did not increase as indicated by changes in plasma protein concentration. The distribution of neurons along the forebrain and brainstem expressing Fos after SO showed the participation of the lamina terminalis, extended amygdala, supraoptic and paraventricular hypothalamic nuclei in the neural network that controls osmoregulatory responses. Both Fos-OT immunoreactive and plasma OT concentration increased after s.c. hypertonic sodium infusion. Finally, matching the “in vivo” electrophysiological study, SO doubled the number of Fos-5HT immunolabeled cells within the DRN. In summary, the results characterize the behavioral, renal and endocrine responses after body sodium overload without volume expansion and specify the cerebral nuclei that participate at different CNS levels in the control of these responses. The electrophysiological approach also allows us to determine in an “in vivo" model that DRN 5HT neurons increase their firing frequency during an increase in systemic sodium concentration and osmolality, possibly to modulate sodium and water intake/excretion and avoid extracellular volume expansion.
Highlights
Under normal volemia conditions, increased natremia or plasma osmolality involves compensatory responses such as water intake, sodium appetite inhibition, plasma release of oxytocin (OT) and vasopressin (AVP), and renal sodium excretion and water retention [1]
Post hoc analysis indicated that the firing rate of putative serotonergic neurons in rats infused with 2 M NaCl increased significantly 3 and 4 minutes after the infusion started compared to the 0.15 M NaCl injected group and to baseline, respectively
The endocrine, renal and behavioral responses were analyzed in the same model and the brain areas and the oxytocinergic PVN-SON groups of neurons activated after a sodium overload were identified
Summary
Under normal volemia conditions, increased natremia or plasma osmolality involves compensatory responses such as water intake, sodium appetite inhibition, plasma release of oxytocin (OT) and vasopressin (AVP), and renal sodium excretion and water retention [1]. The increased natremia and osmolality is centrally detected by the circumventricular organs of the lamina terminalis (CVOs of LT), which have osmo- and sodiumsensitive cells and have shown increased Fos immunoreactivity (Fos-ir) after different paradigms of body salt loading [4,5,6] At brainstem level, this stimulus involved the activity of the lateral parabrachial nucleus (LPBN), locus coeruleus (LC), ventrolateral medulla (VL), nucleus of the solitary tract (NTS) and area postrema (AP). The 5HT agonist (5HT2A/2C, 2,5-dimethoxy-4-iodoamphetamine hydrobromide), injected into the LPBN, increased the renal and endocrine response after EVE and inhibited sodium intake induced by different experimental models [15,16,17,18,19,20] Together these results suggest that body sodium levels modulate the activity of serotonergic DRN cells. The central circuit activated after body sodium overload involves specific nuclei along the brainstem, lamina terminalis, hypothalamic and central extended amygdala areas
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