Although several studies have emphasized a crucial role for the serotonergic system in the control of hippocampal excitability, the role of serotonin (5-Ht) and its receptors in normal and pathologic conditions, such as temporal lobe epilepsy (tLE), is still unclear. the present study was therefore designed firstly to investigate the acute effect of 8-OH-DPAt, a mixed 5-Ht1A/7 receptor agonist, at a high dose (1 mg/kg, i.p.) known to have antiepileptic properties, in a model of acute partial epilepsy in rats. For this purpose, a maximal dentate activation (MDA) pro-tocol was used to measure electrographic seizure onset and duration. In addition, the effect of 8-OH-DPAt on in vivo dentate gyrus cell reactivity and short- and long-term plasticity was studied. Rats injected with 8-OH-DPAt exhibited a significant reduction in MDA and epileptic discharges, a decrease in paired-pulse facilitation and an increase in long-term potentiation. this study suggests that 8-OH-DPAt or in general 5-Ht1A/7 agonists might be use-ful for the treatment of tLE and also have some beneficial effects on the comorbid cognitive disorders seen in epilep-tic patients.