The antiepileptic drug levetiracetam improves auditory gating in DBA/2 mice

Schizophrenia is associated with deficits in P50 gating. This deficit is preclinically modeled in the DBA/2 mouse by depth recordings in the hippocampus. Neurobiologically, the deficit may be due to dysfunction in inhibitory circuitry. It follows that anti-epileptic drugs which impact this circuitry, such as levetiracetam (LEV), may improve gating. To that end, the goal of this study was to evaluate the ability of LEV to normalize sensory gating in the DBA/2 mouse. Gating of the murine analog of the P50, the P20-N40, was evaluated from in vivo hippocampal recordings in 39 male DBA/2 mice. Gating effects were evaluated using four doses of LEV (3, 10, 30, and 100 mg/kg). The 10 mg/kg dose improved P20-N40 gating (P=0.016). No other doses significantly affected gating. Low-dose LEV may improve P20-N40 gating in the DBA/2 mouse model of schizophrenia. Low-doses of LEV may improve P20-N40 gating in the DBA/2 mouse model of schizophrenia and warrant further investigation in the illness.