A functional role for central glucagon-like peptide-1 receptors in lithium chloride-induced anorexia.
The present study sought to determine whether central glucagon-like peptide-1 (GLP-1)-receptor signalling contributes to the anorexigenic effects of systemically administered lithium chloride (LiCl). Male Sprague-Dawley rats with chronic intracerebroventricular (ICV) cannulas were acclimated to a feeding schedule that included daily 30-min access to palatable mash. In the first experiment, ICV infusion of a GLP-1-receptor antagonist [exendin-4-(3-39)] significantly attenuated (10 microgram dose) or completely blocked (20 microgram dose) the inhibition of food intake produced by subsequent ICV infusion of GLP-1-(7-36) amide (5 microgram). In the second experiment, rats were infused with 0, 10, or 20 microgram of the GLP-1-receptor antagonist ICV, followed by injection of 0.15 M LiCl (50 mg/kg ip) or the same volume of 0.15 M NaCl. The ability of LiCl treatment to suppress food intake was significantly attenuated in rats that were pretreated with the GLP-1-receptor antagonist. These results support the view that central mechanisms underlying LiCl-induced anorexia include a prominent role for endogenous GLP-1 neural pathways.
Rinaman
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Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. Rinaman@bns.pitt.edu
D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D007276:Injections, Intraventricular; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000502:physiology*
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D018021:Lithium Chloride