Psychiatric disorders frequently occur in patients with
epilepsy, but the relationship between
epilepsy and psychopathology is poorly understood. Frequent comorbidities in
epilepsy patients comprise major depression,
anxiety disorders,
psychosis and
cognitive dysfunction. Animal models of
epilepsy, such as the
pilocarpine model of acquired
epilepsy, are useful to study the relationship between
epilepsy and behavioral dysfunctions. However, despite the advantages of mice in studying the genetic underpinning of behavioral alterations in
epilepsy, mice have only rarely been used to characterize behavioral correlates of
epilepsy. This prompted us to study the behavioral and cognitive alterations developing in NMRI mice in the
pilocarpine model of
epilepsy, using an anxiety test battery as well as tests for depression,
drug-induced
psychosis, spatial memory, and motor functions. In order to ensure the occurrence of
status epilepticus (SE) and decrease mortality, individual dosing of
pilocarpine was performed by ramping up the dose until onset of SE. This protocol was used for studying the consequences of SE, i.e. hippocampal damage, incidence of
epilepsy with spontaneous recurrent
seizures, and behavioral alterations. SE was terminated by
diazepam after either 60, 90 or 120 min. All mice that survived SE developed
epilepsy, but the severity of hippocampal damage varied depending on SE length. In all anxiety tests, except the elevated plus maze test, epileptic mice exhibited significant increases of anxiety-related behavior. Surprisingly, a decrease in depression-like behavior was observed in the forced swimming and tail suspension tests. Furthermore, epileptic mice were less sensitive than controls to most of the behavioral effects induced by
MK-801 (
dizocilpine). Learning and memory were impaired in epileptic mice irrespective of SE duration. Thus, the
pilocarpine-treated mice seem to reflect several of the behavioral and cognitive disturbances that are associated with
epilepsy in humans. This makes these animals an ideal model to study the neurobiological mechanisms underlying the association between
epilepsy and psychopathology.