In mammals, glycogen synthase kinase-3 (GSK-3) is formed as the two isoforms termed GSK-3α and GSK-3β. GSK-3β is present in a high concentration in the abundance of tissues in the central nervous system, regulating a crucial role in neuronal signaling pathways. The research for involvement of GSK-3β signaling in drug abuse liability has been progressed based on the studies investigating molecular and cellular mechanism of action, but few reports have been made on animal research so far. In this presentation, we demonstrate that pretreatment of mice with CHIR-99021 (5, 10, 15 mg/kg, s.c.), a GSK-3 inhibitor, attenuated methamphetamine (METH)-induced stereotyped behavior (10 mg/kg of METH) in a dose-dependent fashion. Maximal inhibitory effect (ca. 50%) was observed at 10 and 15 mg/kg of CHIR-99021. CHIR-99021 dose-dependently attenuated the expression frequency of METH-induced stereotyped biting whereas CHIR-99021 increased the expression frequency of persistent locomotion. These observations are different results from those of other GSK-3 inhibitors such as SB216763 and AR-A014418, suggesting a possibility of CHIR-99021-specific effect of METH action