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

Although c-Fos induction in the brainstem is a reliable correlate of taste aversion learning and appears necessary for the encoding of the uncondition ed 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 ki nase (MEK) inhibitor PD98059 into the fourth ventricle of mice potently blo cks acquisition of a learned taste aversion. The unconditioned stimulus LiC l produces a rapid and robust phosphorylation of MAP kinase, as revealed by immunohistochemistry with an antibody specific to the dually phosphorylate d active form of MAP kinase. This immunoreactivity is localized to the same region of the intermediate nucleus tractus solitarius in which we have sho wn large increases in c-Fos immunoreactive cells, suggesting that in at lea st a subset of these cells, MAP kinase activation may lead to c-fos inducti on. (C) 2000 Elsevier Science Inc. All rights reserved.