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 receptors are important for control of blood glucose levels. However, rat GLP-1 receptors are also localized in the brain, in hypothalamus, and in areas without a blood-brain barrier. When rats were kept on a food restriction schedule, intracerebroventricular injection of GLP-1 just before food was offered inhibited food intake. However, peripheral GLP-1 administration by intraperitoneal injection had little effect. GLP-1 effects on water intake and output were also investigated. Intracerebroventricular GLP-1 profoundly inhibited angiotensin II-induced drinking behavior in rats, and water intake was suppressed by exogenous GLP-1 in rats habituated to a water restriction schedule. These effects were reproduced by intraperitoneal administration of GLP-1. Furthermore, intracerebroventricular GLP-1 stimulated urinary excretion of water and sodium. The centrally elicited effects were blocked by the GLP-1 antagonist exendin-(9-39) amide, whereas the N-terminally extended and inactive GLP-1-(1-36) amide had no effect on feeding and drinking. GLP-1 had no effect in behavioral assays measuring exploratory locomotor activity and conditioned taste aversion. In conclusion, GLP-1 may play a physiological role in regulation of both ingestion and the water and salt homeostasis.