Abstracts

Rationale: Psychiatric disorders are fairly common comorbidities of epilepsy. The prevalence of psychiatric disorders is around 18-70% depending on the type and severity of epilepsy, being the highest in temporal lobe epilepsy. Apparently, both disorders share related pathogenic mechanisms and can exacerbate each other. Seizures can cause psychiatric disorders, likely due to excessive neuronal discharge, altered brain circuitries and brain damages. Psychiatric disorders can precede the onset of seizures and sometime precipitate seizures. Therefore the relationship between these two diseases is very complex which leads to a great challenge in managing both disorders. Following pilocarpine-induced status epilepticus, rats not only developed spontaneous recurrent seizures, but also exhibited stunning aggressive behavior. Our previous study revealed that rapamycin can suppress chronic spontaneous seizures in the rat pilocarpine model. The present study will examine the effect of rapamycin on neurobehavioral changes using the same model. Methods: Status epilepticus was induced in Sprague-Dawley rats using the lithium chloride and pilocarpine model. Rapamycin was delivered via i.p. injection. Aggressive behavior and chronic seizures were monitored four weeks after pilocarpine injection. The neurobehavioral tests include approach, touch, pick up, and resident-intruder tests which were performed from 9 pm to 12 pm. Chronic spontaneous seizures were monitored via video-EEG recordings. Results: Rapamycin markedly improved aggression in chronic seizure rats. This effect became noticeable within 16-18 hrs following a single dose of rapamycin. Additionally, rats that received rapamycin for three days exhibited a long lasting improvement of aggressive behavior. We observed that this improvement persisted up to 2 weeks after cessation of rapamycin treatment. Afterwards, the aggressive behavior became worse and gradually returned close to the level before rapamycin treatment. By closely monitoring seizure activity, we found that the behavioral improvement occurred in parallel to the decrease in seizure frequency. Conclusions: Our findings provide new insight into the mechanism of psychiatric comorbidity and epilepsy and suggest that rapamycin could be a novel therapeutic paradigm complementary to the existing medication for managing psychiatric disorders associated with epilepsy.