CENTRAL ADMINISTRATION OF GLP-1-(7-36) AMIDE INHIBITS FOOD AND WATER-INTAKE IN RATS

Glucagon-like peptide (GLP)-1-(7-36) amide and its pancreatic receptor s are important for control of blood glucose levels. However, rat GLP- 1 receptors are also localized in the brain, in hypothalamus, and in a reas without a blood-brain barrier. When rats were kept on a food rest riction schedule, intracerebroventricular injection of GLP-1 just befo re food was offered inhibited food intake. However, peripheral GLP-1 a dministration by intraperitoneal injection had little effect. GLP-1 ef fects on water intake and output were also investigated. Intracerebrov entricular GLP-1 profoundly inhibited angiotensin II-induced drinking behavior in rats, and water intake was suppressed by exogenous GLP-1 i n rats habituated to a water restriction schedule. These effects were reproduced by intraperitoneal administration of GLP-1. Furthermore, in tracerebroventricular GLP-1 stimulated urinary excretion of water and sodium. The centrally elicited effects were blocked by the GLP-1 antag onist exendin-(9-39) amide, whereas the N-terminally extended and inac tive GLP-1-(1-36) amide had no effect on feeding and drinking. GLP-1 h ad no effect in behavioral assays measuring exploratory locomotor acti vity and conditioned taste aversion. In conclusion, GLP-1 may play a p hysiological role in regulation of both ingestion and the water and sa lt homeostasis.