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1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP) is a new designer drug of the cathinone type. People who have taken drugs containing α-PVP or other synthetic cathinone reportedly lose consciousness, develop difficulty breathing, and at worst case, die. However, the mechanism underlying α-PVP-induced neurotoxicity is unknown. The objective of the present study was to investigate the effect of α-PVP on the central nervous system (CNS) and compare its neurotoxicity with that of methamphetamine (METH) in mice. Balb/c male mice (8 weeks old) were orally administered α-PVP (25 mg/kg) or METH (5 mg/kg). α-PVP induced a significant increase in locomotor activity, which occurred earlier than locomotor activity induced by METH. This increase was inhibited by the D1 receptor antagonist SCH23990 (50 μg/kg, ip) and the D2 receptor antagonist sulpiride (50 mg/kg, im). The extracellular concentration of dopamine (DA) in the striatum, determined by in vivo microdialysis increased immediately after α-PVP administration. These results suggest that α-PVP stimulates DA release, causing an increase in locomotor activity, and that this stimulatory effect of α-PVP on CNS is mediated, at least in part, by the D1 and D2 receptors.