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We determined if the dorsal raphe nucleus (DRN) exerts tonic control of basal and stimulated sodium and water intake. Male Wistar rats weighing 300-350 g were microinjected with phosphate buffer (PB-DRN, N = 11) or 1 microg/0.2 microl, in a single dose, ibotenic acid (IBO-DRN, N = 9 to 10) through a guide cannula into the DRN and were observed for 21 days in order to measure basal sodium appetite and water intake and in the following situations: furosemide-induced sodium depletion (20 mg/kg, sc, 24 h before the experiment) and a low dose of dietary captopril (1 mg/g chow). From the 6th day after ibotenic acid injection IBO-DRN rats showed an increase in sodium appetite (12.0 +/- 2.3 to 22.3 +/- 4.6 ml 0.3 M NaCl intake) whereas PB-DRN did not exceed 2 ml (P < 0.001). Water intake was comparable in both groups. In addition to a higher dipsogenic response, sodium-depleted IBO-DRN animals displayed an increase of 0.3 M NaCl intake compared to PB-DRN (37.4 +/- 3.8 vs 21.6 +/- 3.9 ml 300 min after fluid offer, P < 0.001). Captopril added to chow caused an increase of 0.3 M NaCl intake during the first 2 days (IBO-DRN, 33.8 +/- 4.3 and 32.5 +/- 3.4 ml on day 1 and day 2, respectively, vs 20.2 +/- 2.8 ml on day 0, P < 0.001). These data support the view that DRN, probably via ascending serotonergic system, tonically modulates sodium appetite under basal and sodium depletion conditions and/or after an increase in peripheral or brain angiotensin II.

The main purpose of this study was to investigate whether dipsogenic stimuli influences the sodium appetite of rats with ibotenic acid lesion of the dorsal raphe nucleus (IBO-DRN). Compared to control, rats microinjected with phosphate buffer (PB-DRN), the ingestion of 0.3M NaCl was enhanced in IBO-DRN at 21 and 35 days after DRN lesion under a protocol of fluids and food deprivation. Despite of similar dipsogenic response observed both in IBO-DRN and PB-DRN treated with isoproterenol (ISO, 300 microg/kg, sc), the 0.3M NaCl intake was again significantly enhanced in IBO-DRN at 21 and 35 days post-lesion. Finally, treatment with polyethylene glycol (PEG, MW=20,000, 20%, w/v, 16.7 ml/kg, sc) induced higher dipsogenic response in IBO-DRN than PB-DRN at 21 day after lesion. In addition, IBO-DRN also expressed higher sodium appetite than PB-DRN, concomitantly with a drinking response. These results suggest that ibotenic lesion of DRN promote an increase of the brain angiotensinergic response, possibly settled within the subfornical organ, through paradigms which increase circulating ANG II levels. The current paper supports the hypothesis that the ibotenic lesion of DRN suppresses a serotonergic component implicated on the modulation of the sodium appetite and, therefore, furthering homeostatic restoration of extracellular fluid volume.

We investigate the influence of brain serotonin depletion on the sodium appetite. Rats depleted of serotonin through the systemic administration of p-chlorophenylalanine (300 mg/kg, ip, for 2 days) showed an intense natriorexigenic response induced by sodium depletion (furosemide, 20 mg/kg, sc, 24 h before water and 1.8% NaCl presentation). Intake of 1.8% NaCl was always higher than that observed for the control group (12.9 +/- 1.4 and 21.4 +/- 3.0 mL vs 5.7 +/- 1.2 and 12.7 +/- 1.6 mL, 30 and 300 min after water and saline presentation). After 24 h, the natriorexigenic response continued to be significantly higher compared to control (33.6+/-5.1 vs 21.9+/-3.6 mL,P <0.05). Fourteen days after p-chlorophenylalanine administration, 1.8% NaCl intake did not differ from controls. Serotonin-depleted rats expressed an early natriorexigenic response after isoproterenol administration on the third day after the first injection of p-chlorophenylalanine. An increase in 1.8% NaCl intake was first observed at 120 min (1.9 +/- 0.2 vs 0.45 +/- 0.3 mL,P <0.05) and remained high up to the end of the 24-h observation period (17.3+/-3.2 vs 1.1+/-0.5 mL,P <0.05). After 7 and 14 days, the natriorexigenic response became comparable to that of control animals. Present results show that brain serotonin depletion exaggerates the sodium appetite induced by the paradigm of sodium depletion or after beta-adrenergic stimulation.

The present study determined the effect of an electrolytic lesion of the dorsal raphe nucleus (DRN) on water intake and sodium appetite. Male Wistar rats weighing 290-320 g with a lesion of the DRN (L-DRN), performed two days before experiments and confirmed by histology at the end of the experiments, presented increased sensitivity to the dehydration induced by fluid deprivation. The cumulative water intake of L-DRN rats reached 23.3 1.9 ml (a 79% increase, N = 9) while sham-lesioned rats (SL-DRN) did not exceed 13.0 1.0 ml (N = 11, P < 0.0001) after 5 h. The L-DRN rats treated with isoproterenol (300 g kg-1 ml-1, sc) exhibited an increase in water intake that persisted throughout the experimental period (L-DRN, 15.7 1.47 ml, N = 9 vs SL-DRN, 9.3 1.8 ml, N = 11, P < 0.05). The L-DRN rats also showed an increased spontaneous sodium appetite during the entire period of assessment. The intake of 0.3 M NaCl after 12, 24, 36 and 72 h by the L-DRN rats was always higher than 20.2 4.45 ml (N = 10), while the intake by SL-DRN was always lower than 2.45 0.86 ml (N = 10, P < 0.00001). Sodium- and water-depleted L-DRN rats also exhibited an increased sodium appetite (13.9 2.0 ml, N = 11) compared to SL-DRN (4.6 0.64 ml, N = 11) after 120 min of observation (P < 0.02). The sodium preference of L-DRN rats in both conditions was always higher than that of SL-DRN rats. These results suggest that electrolytic lesion of the DRN overcomes a tonic inhibitory component of sodium appetite.