Treatment with levetiracetam improves cognition in a ketamine rat model of schizophrenia

Abstract Imbalance in neural excitation and inhibition is associated with behavioral dysfunction in individuals with schizophrenia and at risk for this illness. We examined whether targeting increased neural activity with the antiepileptic agent, levetiracetam, would benefit memory performance in a preclinical model of schizophrenia that has been shown to exhibit hyperactivity in the hippocampus. Adult rats exposed to ketamine subchronically during late adolescence showed impaired hippocampal-dependent memory performance. Treatment with levetiracetam dose-dependently improved memory performance of the ketamine-exposed rats. In contrast, the antipsychotic medication risperidone was not effective in this assessment. Levetiracetam remained effective when administered concurrently with risperidone, supporting potential viability of adjunctive therapy with levetiracetam to treat cognitive deficits in schizophrenia patients under concurrent antipsychotic therapy. In addition to its pro-cognitive effect, levetiracetam was also effective in attenuating amphetamine-induced augmentation of locomotor activity, compatible with the need for therapeutic treatment of positive symptoms in schizophrenia.