Perampanel Attenuates Cognitive and Behavioral Deficits and Modulates Hippocampal Tachykinin Expression in Experimental Temporal Lobe Epilepsy

Background: Epilepsy is one of the most prevalent neurological disorders, often presenting alongside many comorbidities. The present study aimed to evaluate the impact of the antiepileptic drug perampanel (PRM) on cognitive function, depressive-like behavior and the expression of substance P (SP) and neurokinin B (NKB) in the hippocampus of naïve rats and rats with an experimental model of temporal lobe epilepsy (TLE). Methods: Vehicle/PRM (3 mg/kg p. os) was administered 3 h after the induction of status epilepticus by lithium–pilocarpine and continued for the next eleven weeks in Wistar rats. Matched naïve rats were treated with the same doses. Results: Long-term treatment with PRM during the chronic phase of TLE improved passive and active learning and memory, as well as spatial working memory, as measured by the Step-down, Shuttle-box avoidance tests and T-maze test. Additionally, the drug alleviated depressive-like behavior in the sugar preference test and hyperactivity in the Activity cage test. In non-epileptic animals, perampanel did not produce significant alterations in the behavioural parameters assessed. Furthermore, we found that TLE animals exhibited the highest levels of immunoreactivity for both tachykinins SP and NKB. However, perampanel treatment attenuated these elevations to varying degrees, depending on the hippocampal region. This was particularly evident in the CA3 subfield and the granular layer of the dentate gyrus. In non-epileptic animals, perampanel produced only minor changes relative to vehicle-treated controls. In conclusion, the observed cognitive improvement and antidepressant-like behavior associated with perampanel are presumed to result from its impact on the hippocampal tachykinin expression.