Pathways of Fos expression in locus ceruleus, dorsal vagal complex, and PVN in response to intestinal lipid

Am J Physiol. 1997 Dec;273(6):R2059-71. doi: 10.1152/ajpregu.1997.273.6.R2059.


Exogenous cholecystokinin (CCK) injected peripherally mimics effects of lipid entering the intestine on food intake and gastric motility via vagal afferents and induces c-fos expression in the locus ceruleus complex (LCC), nucleus of the solitary tract (NTS), area postrema (AP), and paraventricular nucleus (PVN). However, the role of peripheral endogenous CCK in induction of c-fos expression in the brain at ingestion of nutrients is controversial. In awake rats, intraduodenal lipid infusion markedly increased Fos protein-like immunoreactivity (FLI) in these brain nuclei. Perivagal capsaicin pretreatment reduced the increase of FLI in the LCC, NTS, and PVN by 66-86% and in the AP by 46%. The CCK-A receptor antagonist MK-329 (0.1 mg/kg i.p.) diminished the FLI increase in LC, NTS, AP, and PVN by 39-100%; the CCK-B receptor antagonist L-365,260 reduced the increased FLI in the AP by 54%. After capsaicin pretreatment, both CCK antagonists had additional inhibitory effects only on FLI in the AP. These findings suggest that entry of lipid into the intestine activates c-fos in the LCC, NTS, and PVN predominantly via CCK-A receptors on vagal afferents and in the AP via vagal and nonvagal pathways, as well as CCK-B and CCK-A receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodiazepinones / pharmacology
  • Capsaicin / pharmacology
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / metabolism
  • Cholecystokinin / blood*
  • Devazepide
  • Duodenum / physiology*
  • Enteral Nutrition
  • Fat Emulsions, Intravenous / administration & dosage
  • Fat Emulsions, Intravenous / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Hormone Antagonists / pharmacology
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / metabolism*
  • Male
  • Mannitol / pharmacology
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Phenylurea Compounds*
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cholecystokinin A
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin / antagonists & inhibitors
  • Solitary Nucleus / drug effects
  • Solitary Nucleus / metabolism
  • Vagus Nerve / drug effects
  • Vagus Nerve / metabolism*


  • Benzodiazepinones
  • Fat Emulsions, Intravenous
  • Hormone Antagonists
  • Phenylurea Compounds
  • Proto-Oncogene Proteins c-fos
  • Receptor, Cholecystokinin A
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin
  • L 365260
  • Mannitol
  • Cholecystokinin
  • Devazepide
  • Capsaicin