Postictal symptoms can be disabling in themselves, but their underlying substrates may endure, giving rise to
epilepsy-induced interictal behavioral disorders. Chronic
temporal lobe epilepsy is reported to be associated with a variety of interictal behavioral changes which often take the form of affective disturbances. Depression, among the more common interictal psychological dysfunctions suffered by patients with temporal lobe
seizures, could reflect
epilepsy-induced alterations in normal
opioid peptide mechanisms. In experimental animal models, certain postictal behaviors have been shown to be
opioid-mediated. Furthermore, an experimental model of interictal behavioral disturbance resembles stimulation-induced defensive rage, which can be relieved by intracerebral administration of
opioid peptides. Defensive rage is a species-specific behavior encountered in cats. Its correlate in humans would be difficult to predict in view of the stronger cortical control; however, it may manifest rather as insecurity, irritability, and perhaps depression. Extrapolation of animal experiments would suggest that depression and certain other common postictal and interictal affective disturbances seen in patients with temporal lobe
seizures reflect mechanisms more related to
opiate withdrawal, than to direct
opiate actions. The activity-induced plasticity associated with recurrent temporal lobe
seizures, therefore, should result in changes in
opioid function that predispose to withdrawal phenomena. Limbic
seizures induce enhanced
enkephalin synthesis lasting for up to 2 weeks. Recurrent
seizures in experimental animals, however, cause paradoxical up-regulation of mu
opiate receptors. Patients with
temporal lobe epilepsy demonstrate enhanced
mu receptor binding in the neocortex of the epileptogenic temporal lobe on PET. The reasons for this enduring interictal effect are not clear. Nevertheless, if animals or patients become dependent on enhanced endogenous
opioid activity as a result of
seizures, and also have up-regulation of
mu receptors, then severe withdrawal effects, such as defensive rage in cats or depression in humans, might be expected when
seizures do not recur frequently. Plotting the time course of mRNAenk and
enkephalin expression after
seizures, and the time course of symptoms of interictal behavioral disturbances, may demonstrate a temporal relationship that supports this hypothesis. For instance, depression or other
withdrawal symptoms might only occur when the interval between
seizures is greater than the duration of seizure-induced
enkephalin synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)