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The Journal of Neuroscience, December 1, 2002, 22(23):10470-10476
The Diverse Roles of Specific GLP-1 Receptors in the Control of Food Intake and the Response to Visceral Illness
Kimberly P. Kinzig1, David A. D'Alessio2, and Randy J. Seeley1 Departments of 1 Psychiatry and 2 Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0559
Intracerebroventricular administration of glucagon-like peptide-1 (7-36) amide (GLP-1) reduces food intake and produces symptoms of visceral illness, such as a conditioned taste aversion (CTA). The central hypothesis of the present work is that separate populations of GLP-1 receptors mediate the anorexia and taste aversion associated with GLP-1 administration. To test this hypothesis, we first compared the ability of various doses of GLP-1 to induce anorexia or CTA when administered into either the lateral or fourth ventricle. Lateral and fourth ventricular GLP-1 resulted in reduction of food intake at similar doses, whereas only lateral ventricular GLP-1 resulted in a CTA. Such data indicate that both hypothalamic and caudal brainstem GLP-1 receptors are likely to participate in the ability of GLP-1 to reduce food intake. We also hypothesized that the site that must mediate the ability of GLP-1 to induce visceral illness is in the central nucleus of the amygdala (CeA). Administration of 0.2 or 1.0 µg of GLP-1 (7-36) but not the inactive GLP-1 (9-36) resulted in a strong CTA with no accompanying anorexia. In addition, bilateral CeA administration of 2.5 µg of a GLP-1 receptor antagonist before intraperitoneal administration of the toxin lithium chloride resulted in a diminished CTA. Together, these data indicate that separate GLP-1 receptor populations mediate the multiple responses to GLP-1. These results indicate that GLP-1 is a flexible system that can be activated under various circumstances to alter the ingestion of nutrients and/or produce other visceral illness responses, depending on the ascending pathways of the GLP-1 system that are recruited.
Key words: conditioned taste aversion; GLP-1; food intake; visceral illness; central nucleus of the amygdala; hypothalamus
Copyright © 2002 Society for Neuroscience 0270-6474/02/222310470-07$05.00/0
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