Aims: 

The effects of the centrally administered neuropeptides orexin-A and -B on water intake and vasopressin (VP) secretion were studied in rats.

Methods: 

Male Wistar rats (200–250g) were used. A cannula was implanted into the lateral ventricle. Different doses of orexins were administered (10–30–90mg/10ml) intracerebroventricularly (i.c.v.) under anaesthesia. Water consumption was measured for 6 hours. As the 30mg/10ml dose of orexin-A proved most efficient, this dose of orexin-A was administered subsequently. A VP level elevation was induced by histamine (10mg/kg) and 2.5% NaCl (10ml/kg) administered intraperitoneally (i.p.) 15 minutes after orexin administration. The orexin-1 receptor (OX1) antagonist was used in a dose of 3mg/kg i.p., 30 minutes before neuropeptide administration. Plasma VP levels were measured by RIA.

Results: 

10mg/10ml orexin-A or orexin-B did not increase the water intake. Increased water consumption was observed after the administration of 30mg/10ml orexin-A (11.4±0.86ml vs. control: 2.73±0.391ml). There were no changes in basal VP secretion after the administration of different doses of the orexins (5.8±0.45pg/ml). A significant increase in vasopressin concentration was detected following histamine (59.03±1.98pg/ml) administration. After 2.5% NaCl administration a moderate VP level enhancement was detected (23.65±2.47pg/ml). I.c.v. orexin-A (30mg/10ml) blocked the increased VP level induced by histamine or hyperosmosis (6.3±0.048pg/ml). The inhibitory effects were prevented by the specific OX1 antagonist.

Conclusions: 

1.Orexin-A or orexin-Bdose-dependently increased the water consumption. After orexin-A administration, the polydipsia was more pronounced. The OX1 antagonist decreased the water consumption significantly. 2. Histamine or hyperosmotic VP release enhancement was blocked by i.c.v. orexin administration. This inhibition was not observed following OX1 antagonist administration. 4. Our results suggest that the effect of orexin on water consuption or blockade of the histamine and osmotic-induced VP level increase is mediated by the OX1 receptor.

Support: 

SROP4.2.2.-08/1-2008-0006, János Bolyai Research Scholarship of the Hungarian Academy of Sciences