Summary: Purpose: To study seizure‐induced changes in signaling proteins present in postsynaptic densities (PSDs) isolated from human epileptic neocortex and from rat cortex in which seizures were induced by injection of kainic acid. Methods: We performed Western blot analysis of signaling proteins in PSDs isolated from cortical tissue. Results: Seizures induce a strong upregulation of TrkB, the receptor for brain‐derived neurotrophic factor (BDNF), whereas components of the N ‐methyl‐ d ‐aspartate (NMDA)‐receptor complex are downregulated in both human and rat PSDs. Conclusions: These data show that long‐term changes in PSD composition occur as a consequence of epileptic seizure activity.