Central Infusion of Glucagon-Like peptide-1-(7-36) Amide (GLP-1) Receptor Antagonist Attenuates Lithium Chloride-Induced c-Fos Induction in Rat Brainstem

Brain Res. 1998 Aug 10;801(1-2):164-70. doi: 10.1016/s0006-8993(98)00584-8.

Abstract

Central infusion of glucagon-like peptide-1-(7-36) amide (GLP-1) and intraperitoneal (i.p.) injection of lithium chloride (LiCl) produce similar patterns of c-Fos induction in the rat brain. These similarities led us to assess the hypothesis that neuronal activity caused by i.p. injection of LiCl involves activation of central GLP-1 pathways. We therefore determined if third-ventricular (i3vt) infusion of a GLP-1 receptor antagonist would block LiCl-induced c-Fos expression in the brainstem. Relative to rats pretreated with i3vt infusion of vehicle, pretreatment with the potent GLP-1 receptor antagonist, des His1 Glu9 exendin-4 (10.0 microgram), significantly attenuated LiCl-induced (76 mg/kg; i.p.) c-Fos expression in several brainstem regions, including the area postrema, the nucleus of the solitary tract, and the lateral parabrachial nucleus. While central infusion of des His1 Glu9 exendin-4 also blocked GLP-1-induced (10.0 microgram) anorexia and c-Fos expression, the antagonist produced no independent effects on food intake or c-Fos expression. These results suggest that LiCl-induced c-Fos expression in the rat brainstem is mediated, at least in part, by GLP-1 receptor signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Stem / chemistry
  • Brain Stem / drug effects*
  • Brain Stem / metabolism
  • Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptides
  • Guinea Pigs
  • Infusions, Parenteral
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Insulin / analysis
  • Insulin / metabolism
  • Insulin Secretion
  • Insulinoma
  • Lithium Chloride / administration & dosage
  • Lithium Chloride / pharmacology*
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Proto-Oncogene Proteins c-fos / drug effects
  • Rats
  • Rats, Long-Evans
  • Receptors, Glucagon / antagonists & inhibitors*
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured

Substances

  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Insulin
  • Peptide Fragments
  • Proto-Oncogene Proteins c-fos
  • Receptors, Glucagon
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Lithium Chloride