Spreading depression (SD) is assumed to play a critical role in a number of clinical disorders including epilepsy. SD has also been observed in a variety of in vitro and in vivo epilepsy models in different animal species as well as in epileptic patients. The aim of present study is to evaluate the possible role of SD in triggering epileptiform field potentials (EFP) in temporal lobe structures. Combined amygdala-hippocampus–cortex slices were prepared by horizontal cut of the rat brain. SD, induced by KCl injection in temporal neocortex, amygdala, or hippocampus, propagated in various parts of slices by different patterns. After addition of low concentration of GABAA receptor antagonist bicuculline (1.25 mmol/l) to the superfusate for 45 minutes, induction of SD triggered EFP (both ictal and interictal activities) in all tested slices. Patterns of EFP propagation and its onset latency as well as the form of burst discharges varied based on the site of SD initiation. Among different antiepileptic drugs, lamotrigine was the most potent substance which inhibited triggering of EFP by SD. The results indicate that SD increases the neuronal excitability in different structures of temporal lobe and triggers the seizure-like activities.