As an endogenous inhibitor of glutamate-mediated synaptic transmission in mammalian central nervous system, neuropeptide Y (NPY) plays a crucial role in regulating homeostasis of neuron excitability.Loss of balance between excitatory and inhibitory neurotransmission is thought to be a chief mechanism of epileptogenesis.The abnormal expression of NPY and its receptors observed following seizures have been demonstrated to be related to the production of epilepsy.The tremor rat (TRM) is a hereditary epileptic animal model.So far, there is no report conceming whether NPY and its receptors may be involved in TRM pathogenesis.In this study, we focused on the expression of NPY and its three receptor subtypes: Y1R, Y2R and Y5R in the TRM brain.We first found the expression of NPY in TRM hippocampus and temporal lobe cortex was increased compared with control (Wistar) rats.The mRNA and protein expression of Y1R was down-regulated in hippocampus but up-regulated in temporal lobe cortex, whereas Y2R expression was significantly increased in both areas.There was no significant change of Y5R expression in either area.The immunohistochemistry data showed that Y1R, Y2R, Y5R were present throughout CA1, CA3, dentate gyrus (DG) and the entorhinal cortex which is included in the temporal lobe cortex of TRM.In conclusion, our results showed the altered expression of NPY, Y1R and Y2R but not Y5R in hippocampus and temporal lobe cortex of TRM brain.This abnormal expression may be associated with the generation of epileptiform activity and provide a candidate target for treatment of genetic epilepsy.