CENTRAL INFUSION OF GLUCAGON-LIKE PEPTIDE-1-(7-36) AMIDE (GLP-1) RECEPTOR ANTAGONIST ATTENUATES LITHIUM CHLORIDE-INDUCED C-FOS INDUCTION INRAT BRAIN-STEM

Central infusion of glucagon-like peptide-1-(7-36) amide (GLP-1) and i ntraperitoneal (i.p.) injection of lithium chloride (LiCl) produce sim ilar 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 th erefore determined if third-ventricular (i3vt) infusion of a GLP-1 rec eptor antagonist would block LiCl-induced c-Fos expression in the brai nstem. Relative to rats pretreated with i3vt infusion of vehicle, pret reatment with the potent GLP-1 receptor antagonist, des His(1) Glu(9) exendin-4 (10.0 mu g), significantly attenuated LiCl-induced (76 mg/kg ; i.p.) c-Fos expression in several brainstem regions, including the a rea postrema, the nucleus of the solitary tract, and the lateral parab rachial nucleus. While central infusion of des His(1) Glu(9) exendin-4 also blocked GLP-1-induced (10.0 mu g) anorexia and c-Fos expression, the antagonist produced no independent effects on food intake or c-Fo s 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. (C) 1998 Elsevier Science B.V. All rights reserved.