Pharmacological antagonism of tyrosine kinases and MAP kinase in brainstem blocks taste aversion learning in mice

Physiol Behav. 2000 Jun 1-15;69(4-5):499-503. doi: 10.1016/s0031-9384(00)00225-0.


Although c-Fos induction in the brainstem is a reliable correlate of taste aversion learning and appears necessary for the encoding of the unconditioned stimulus, little is known about the intracellular signaling pathways in the brainstem that regulate c-Fos expression during taste aversion learning. Infusion of the tyrosine kinase inhibitor genistein and the MAP kinase kinase (MEK) inhibitor PD98059 into the fourth ventricle of mice potently blocks acquisition of a learned taste aversion. The unconditioned stimulus LiCl produces a rapid and robust phosphorylation of MAP kinase, as revealed by immunohistochemistry with an antibody specific to the dually phosphorylated active form of MAP kinase. This immunoreactivity is localized to the same region of the intermediate nucleus tractus solitarius in which we have shown large increases in c-Fos immunoreactive cells, suggesting that in at least a subset of these cells, MAP kinase activation may lead to c-fos induction.

Publication types

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

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Brain Stem / enzymology*
  • Brain Stem / physiology
  • Drug Antagonism
  • Enzyme Inhibitors / administration & dosage
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Lithium Chloride / administration & dosage
  • MAP Kinase Kinase Kinase 1*
  • Male
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Saccharin / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Sodium Chloride / administration & dosage
  • Solitary Nucleus / drug effects
  • Solitary Nucleus / enzymology
  • Taste / physiology*


  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-fos
  • Sodium Chloride
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • Map3k1 protein, mouse
  • Saccharin
  • Lithium Chloride