An isolated epileptic seizure elicits learning impairment which could be prevented by melatonin

► A short generalized tonic-clonic seizure impairs learning in Morris water maze. ► Fluctuation of oxidative stress may be important in spatial learning impairment. ► Preconditioning by hypoxia or pre-treating with melatonin improves performance. ► Preconditioning by hypoxia changes behavioral pattern before the onset of seizure. ► Suppression of oxidative stress may be beneficial in clinical epileptology.