The role of CNS glucagon-like peptide-1 (7-36) amide receptors in mediating the visceral illness effects of lithium chloride.
Peripheral administration of large doses of lithium chloride (LiCl) to rats causes a spectrum of effects that are consistent with visceral illness. LiCl reduces food intake, decreases salt ingestion after sodium depletion, induces pica, and produces robust conditioned taste aversions. Because some of the effects of peripheral LiCl are mimicked by centrally administered glucagon-like peptide-1 (7-36) amide (GLP-1), we hypothesized that this peptide is involved in the neural pathways by which LiCl causes visceral illness. To test this hypothesis, we pretreated rats with a selective and potent GLP-1 receptor antagonist given directly into the third ventricle via an indwelling cannula before administration of peripheral LiCl. The GLP-1 receptor antagonist completely blocked the effect of LiCl to reduce food intake, induce pica, and produce a conditioned taste aversion. The same dose of GLP-1 receptor antagonist did not reverse the LiCl-induced reduction in NaCl intake. The data indicate a role for GLP-1 receptors in the CNS pathway that mediates some of the effects of visceral illness.
Seeley
R J
RJ
Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0559, USA. seeleyrj@email.uc.edu
Blake
K
K
Rushing
P A
PA
Benoit
S
S
Eng
J
J
Woods
S C
SC
D'Alessio
D
D
D000809:Angiotensins / Q000008:administration & dosage; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004327:Drinking Behavior / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D005934:Glucagon / Q000502:physiology; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D007276:Injections, Intraventricular; D007616:Kaolin / Q000494:pharmacology; D018021:Lithium Chloride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000502:physiology*; D012982:Sodium, Dietary; D013649:Taste / Q000187:drug effects*; D013997:Time Factors
D000809:Angiotensins; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D018027:Receptors, Glucagon; D012982:Sodium, Dietary; C055453:glucagon-like peptide 1 (7-36)amide; D007616:Kaolin; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D018021:Lithium Chloride