Levetiracetam produces anxiolytic-like effects and attenuates the adverse consequences of stress exposure in mice

Levetiracetam, a second-generation antiepileptic drug, is proposed to regulate neurotransmitter release, including glutamate, by inhibiting the synaptic protein SV2A, as well as modulating voltage-gated calcium channels and reducing excessive synaptic vesicle exocytosis. It may also influence the activity of Kv3.1 channels, which play a critical role in maintaining the fast-spiking activity of parvalbumin-expressing GABAergic interneurons. Through these mechanisms, levetiracetam may help restore the excitatory/inhibitory (E/I) balance, which is often disrupted in psychiatric disorders. Here, we investigated whether acute levetiracetam (50, 100, and 150 mg/kg) produces anxiolytic- and antidepressant-like effects and attenuates the expression and extinction of contextual fear conditioning, as well as cognitive deficits induced by a single footshock exposure in male C57BL/6 mice. Levetiracetam produced an anxiolytic-like effect in the elevated plus-maze, reduced fear expression, and mitigated cognitive impairments in the object recognition test following single footshock exposure. These results suggest that, in addition to its antiepileptic properties, levetiracetam may have therapeutic potential for treating stress-related abnormalities in emotional regulation and cognitive processing.