Behavioral, biochemical and histological studies in a model of pilocarpine-induced spontaneous recurrent seizures

Although the presence of profound cognitive disturbances in lithium-pilocarpine-induced spontaneous recurrent seizures (SRS) has been well documented, much less is known about changes in emotional behavior, in this model of temporal lobe epilepsy. To that end, a lithium-pilocarpine model of SRS was used to evaluate behavior of experimental animals (SRS, non-SRS and saline-treated rats) in different tests of anxiety (open field test, fear conditioning freezing and footshock-induced ultrasonic vocalization). Flinch-jump test, allowing determination of pain threshold, was employed to confirm specificity of data from anxiety tests. Moreover, neurotransmitters' (dopamine, serotonin and their metabolites) concentration was measured in selected brain structures involved in emotional and motor processing (hippocampus, frontal cortex and striatum). Finally, different brain structures were examined histologically in order to determine structures likely to be involved in behavioral changes. It was found that SRS rats, tested in a seizure free period, revealed an increase in motor activity, and a decrease in fear-related reactions (a freezing response to the aversively conditioned context, and a spontaneous, emotion-related ultrasonic vocalization). No changes in the pain threshold were present. The activity of dopamine and serotonin systems in examined brain structures remained unchanged. The neuropathological effects were widespread and involved a loss of neurons, proliferation of astroglial cells and the presence of activated ramified and ameboid microglial cells in the hippocampus proper, piriform cortex, amygdala and lateral posterior thalamic nuclei. The obtained results suggest a prevalence of disinhibitory effects on behavior in SRS rats, as shown by the results of contextual fear and aversive vocalization tests (i.e. a release of rat behavior controlled by fear). It is conceivable that the lesions to the limbic structures involved in the origin of emotions; the hippocampus, amygdala, and piriform cortex, may underlie changes in anxiety reactions in SRS rats. These results indicate that lithium-pilocarpine-induced SRS are also accompanied by profound alteration of animal emotional behavior.