Anxiogenic-like consequences in animal models of complex partial seizures

Several kinds of psychiatric symptoms (anxiety, depression, schizophrenia) have been associated with epilepsies, and clinical data suggest that patients with seizures involving limbic structures are the most prone to develop behavioural disorders between the seizures (i.e. interictally). Studying the neurobiological mechanisms that underlie these symptoms is difficult in humans because of different interfering factors (e.g. psychosocial difficulties, pharmacological side-effects, lesions), which can be avoided in animal models. Using repetitive electrical stimulations (kindling) or local applications of a neuroexcitotoxin in limbic structures (mainly the amygdala and hippocampus), several authors have reported lasting changes of emotional reactivity in cats and rats. These changes appear as anxiety-related reactions expressed as a hyperdefensiveness in the cat, or a reduction of spontaneous exploration in tests predictive of anxiogenic effects in the rat. Some neuroplasticity processes known to develop during epileptogenesis (neuronal-hyperexcitability, modulation of GABA/benzodiazepine transmission) may participate in these lasting changes of behaviour, especially in structures involved in the control of fear-promoted reactions (amygdala, periaqueductal grey matter). In addition, endogenous control systems may also play a critical role in the occurrence of interictal behavioural disorders.