Seizure threshold increases during a series of electroconvulsive therapy (ECTs). Based on assumptions that the effect of ECT may be related to its anticonvulsant effect we were interested in identifying transmitters that are activated by the treatment and play an anticonvulsant role. Animal studies reveal that neuropeptide Y (NPY) neurotransmission is increased by repeated electroconvulsive shock (ECS), and NPY has been found to inhibit glutamate-mediated synaptic transmission in the rat hippocampus. The increase of NPY gene expression in highly sensitive areas of the rat hippocampus (dentate gyrus) and piriform cortex accompanied by a reduction of NPY binding sites in the same regions after ECS supports this notion. Further studies have shown that NPY exerts a seizure-suppressing activity of NPY after kainic acid injections in vivo. Taken together the present series of experiments in rats strongly points to the seizure suppressing properties of NPY and suggests that this peptide may be involved in the seizure threshold increase during effective ECT in humans.