Synthesis of the neurotrophic factor brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus have been proposed to be influenced by endogenous glutamate. To test this hypothesis we have investigated if increases in BDNF and trkB mRNAs are associated with changes in the synaptic release of glutamate in the dorsal hippocampus in the conscious rat by combining the technique of in vivo microdialysis with in situ hybridization histochemistry. A 35% and 66% increase in extracellular levels of glutamate in the dorsal CA1 region was detected following injection into the lateral entorhinal cortex of 2.4 and 9.6 microg of the non-NMDA glutamate receptor agonist quisqualate, respectively. The increase in glutamate was attenuated by local administration of tetrodotoxin (TTX) indicating neuronal origin. Levels of BDNF and trkB mRNAs were increased in the hippocampus in a dose-dependent fashion following the stimulations. The extracellular levels of glutamate in individual animals correlated to the levels of BDNF and trkB mRNAs in the dorsal CA1 region of the hippocampus. This study provides for the first time evidence of an entorhinal cortex influenced concentration-dependent relationship between the release of endogenous glutamate in vivo and neuronal expression of mRNAs for BDNF and its receptor trkB in the hippocampus.