RESUMEN
We investigated the possible role of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus (DRN) on salt intake response during basal conditions and following natriorexigenic challenge aroused by sodium depletion in rats. Acute systemic administration (76-1520 nmol/kg s.c.) of 8-OH-DPAT, a selective 5-HT(1A) somatodendritic autoreceptor agonist, induced a clear and dose-dependent preference for salt intake through free choice between water and 0.3 M NaCl simultaneously offered under basal conditions. Acute intra-DRN microinjection (7.5 nmol/rat) of 8-OH-DPAT significantly mimicked the acute systemic protocol in sodium-replete rats. Interestingly, microinjection of 8-OH-DPAT into the DRN raised an additional long-lasting increase of 0.3 M NaCl intake in sodium-depleted rats despite a high volume ingested 30 min after central injection. Conversely, chronic systemic treatment (1520 nmol/kg s.c.) with 8-OH-DPAT for 2 and 3 weeks or repeated intra-DRN microinjection (7.5 nmol/rat) evoked a significant long-term decrease in 0.3 M NaCl intake in sodium-depleted rats given only water and a sodium-deficient diet over the course of 24 h after furosemide injection. These results show a clear-cut involvement of the DRN 5-HT(1A) somatodendritic autoreceptors in sodium satiety signaling under basal conditions and during the consummatory phase of salt intake in sodium-depleted rats.
Asunto(s)
Autorreceptores/fisiología , Núcleos del Rafe/metabolismo , Receptor de Serotonina 5-HT1A/metabolismo , Respuesta de Saciedad/fisiología , Cloruro de Sodio Dietético/metabolismo , Equilibrio Hidroelectrolítico/fisiología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Autorreceptores/efectos de los fármacos , Dendritas/efectos de los fármacos , Dendritas/metabolismo , Dendritas/ultraestructura , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Esquema de Medicación , Furosemida/farmacología , Masculino , Microinyecciones , Puente/citología , Puente/efectos de los fármacos , Puente/metabolismo , Núcleos del Rafe/citología , Núcleos del Rafe/efectos de los fármacos , Ratas , Ratas Wistar , Respuesta de Saciedad/efectos de los fármacos , Agonistas del Receptor de Serotonina 5-HT1 , Agonistas de Receptores de Serotonina/farmacología , Cloruro de Sodio/metabolismo , Cloruro de Sodio/farmacología , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacología , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
We investigated the effects of chronic administration of sertraline (SERT; approximately 20 mg kg(-1) day(-1) in drinking water), a selective serotonin reuptake inhibitor, on water and sodium intake and on plasma levels of oxytocin (OT) and vasopressin (AVP) in basal and stimulated conditions. Basal water intake was reduced in SERT-treated rats. After 24 h of water deprivation, rats treated with SERT for 21 days ingested less water than the control rats (9.7 +/- 0.5 versus 20.0 +/- 0.9 ml, respectively, at 300 min after water presentation, P < 0.0001). Subcutaneous injection of 2 m NaCl or isoproterenol evoked a lower dipsogenic response in rats treated with SERT for 21 days. Fluid and food deprivation also induced a weaker dipsogenic response in SERT-treated rats (1.6 +/- 0.5 versus 10.2 +/- 1.2 ml, at 300 min, P < 0.0001) but had no effect on saline intake. Sodium depletion induced a higher natriorexigenic response in the SERT group (5.6 +/- 1.3 versus 1.2 +/- 0.3 ml, at 300 min, P < 0.0002). Higher urinary density and lower plasma sodium levels were observed after SERT treatment. Sertraline also increased plasma levels of vasopressin and oxytocin (AVP, 2.65 +/- 0.36 versus 1.31 +/- 0.16 pg ml(-1), P < 0.005; OT, 17.16 +/- 1.06 versus 11.3 +/- 1.03 pg ml(-1), P < 0.0009, at the third week post-treatment). These data constitute the first evidence that chronic SERT treatment affects water and sodium intake in rats. These effects seem to be related to the hyponatraemia caused by the higher plasma levels of AVP and OT.