Genetically epilepsy-prone rats (GEPR-9s) were derived from Sprague-Dawley rats (SD). The number of kainate-induced wet dog shake behavior (WDS) responses was found to decrease significantly in GEPR-9s compared to SD. WDS responses were potentiated by 5-hydroxytryptophan or 2,5-dimethoxy-4-iodoamphetamine and antagonized by ritanserin. The antagonizing effect of ritanserin on WDS latency was more evident in GEPR-9s than in SD, and hippocampal expression of activity-regulated cytoskeleton-associated protein paralleled the severity of WDS. The results suggest that downstream serotonergic synaptic activation is less pronounced in GEPR-9s than in SD and that the serotonergic agent may directly activate postsynaptic 5-HT2A receptors in both strains.