Synaptic vesicle glycoprotein 2A (SV2A) is specifically expressed in synaptic vesicles and regulates neurotransmitter release at synapses. Recent studies reported a significant association of genetic SV2A polymorphism with schizophrenia (Schizophr. Res., 141, 262, 2012). We performed behavioral study using the SV2A-mutant rats, which carry a loss-of-function mutation (L174Q) in the Sv2a gene, to elucidate the effect of levetiracetam (LEV, a SV2A ligand) on methamphetamine (MAP)-induced hyperactivity in Sv2a L174Q rats. Acute treatments with MAP (1 mg/kg, i. p.) significantly increased locomotor activities in Sv2a L174Q rats, but not in control (F344) rats. The MAP-induced hyperactivity in Sv2a L174Q rats was weakly potentiated by LEV (30 mg/kg, i.p.). In F344 rats, LEV markedly potentiated MAP-induced hyperactivity to the extent similar to Sv2a L174Q rats. In addition, D 2 blocker, haloperidol (0.3 mg/kg, i.p.) completely suppressed the augmentation of MAP-induced hyperactivity by LEV in both Sv2a L174Q and F344 rats. The present results suggest that dysfunction of SV2A induces behavioral supersensitivity to MAP by increasing dopamine release, which may be linked to vulnerability against schizophrenia. Further, LEV reduces the function of SV2A, suggesting that LEV may exacerbate psychiatric symptoms.