Rinaman, Linda, and Elizabeth E. Rothe. GLP-1 receptor signaling contributes to anorexigenic effect of centrally administered oxytocin in rats. Am J Physiol Regulatory Integrative Comp Physiol 283: R99-R106, 2002. First published March 29, 2002 10.1152/ajpregu.00008.2002.-The present study examined possible interactions between central glucagon-like peptide-1 (GLP-1) and oxytocin (OT) neural systems by determining whether blockade of GLP-1 receptors attenuates OT-induced anorexia and vice versa. Male rats were acclimated to daily 4-h food access. In the first experiment, rats were infused centrally with GLP-1 receptor antagonist or vehicle, followed by an anorexigenic dose of synthetic OT. Access to food began 20 min later. Cumulative food intake was measured every 30 min for 4 h. In the second experiment, rats were infused with OT receptor blocker or vehicle, followed by synthetic GLP-1 [(7-36) amide]. Subsequent food intake was monitored as before. The anorexigenic effect of OT was eliminated in rats pretreated with the GLP-1 receptor antagonist. Conversely, GLP-1-induced anorexia was not affected by blockade of OT receptors. In a separate immunocytochemical study, OT-positive terminals were found closely apposed to GLP-1-positive perikarya, and central infusion of OT activated c-Fos expression in GLP-1 neurons. These findings implicate endogenous GLP-1 receptor signaling as an important downstream mediator of anorexia in rats after activation of central OT neural pathways. food intake; paraventricular nucleus of the hypothalamus; dorsal vagal complex CENTRAL INFUSION of either synthetic oxytocin (OT) or glucagon-like peptide-1 (GLP-1) inhibits deprivationinduced food intake in rats (1,2,13,28,30,31). Hypothalamic OT-and hindbrain GLP-1-containing neurons are activated in rats after various treatments that promote anorexia; such treatments include systemic administration of lithium chloride, lipopolysaccharide, or cholecystokinin octapeptide (16,17,19,32). Furthermore, pharmacological studies provided evidence that central OT and GLP-1 receptor signaling pathways contribute to the anorexigenic effects of several such treatments (5,14,15,25).OT neurons that project to sites within the brain are located in parvocellular subnuclei of the paraventricular nucleus of the hypothalamus (PVN) (27). GLP-1 neurons are located in the hindbrain, within and near caudal levels of the dorsal vagal complex (DVC) (8, 9, 11). Direct, reciprocal neural connections exist between the hypothalamic and hindbrain regions where OT and GLP-1 neurons are located (19,20,24,26). Hypothalamic OT neurons express GLP-1 receptors (12, 33), and central administration of GLP-1 activates c-Fos expression in OT neurons (10). These findings suggest that the anorexigenic effect of centrally administered GLP-1 might result from activation of OT neurons and signaling pathways originating in the PVN. The present study was initiated to test this hypothesis. However, we also considered the possibility that the anorexigenic effect of centrally administer...