Kindling epileptogenesis in immature rats leads to persistent depressive behavior.

Depression is a frequent comorbidity in epilepsy patients. A variety of biological factors may underlie epilepsy-associated depression. We examined whether kindling-induced chronic increase in seizure susceptibility is accompanied by behavioral symptoms of depression. Three-week-old Wistar rats underwent rapid kindling: 84 initially subconvulsant electrical stimulations of ventral hippocampus delivered every 5 minutes, followed by depression-specific behavioral tests performed 2 and 4 weeks later. Kindled animals exhibited a sustained increase in immobility time in the forced swim test and the loss of taste preference toward calorie-free saccharin, as compared with controls. Initial loss of preference toward the intake of calorie-containing sucrose was followed by the increased consumption at 4 weeks. At both time points, animals exhibited enhanced seizure susceptibility on test stimulations of the hippocampus. We conclude that neuronal plastic changes associated with the kindling state are accompanied by the development of depressive behavior.