Glycogen synthase kinase-3 (GSK-3) is one of the most essential serine/threonine kinases, which are constitutively active, multifaceted, and ubiquitous in nature. In mammalian cells, GSK-3 is formed as the two isoforms termed GSK-3alpha and GSK-3beta. GSK-3beta 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-3beta 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 will demonstrate that pretreatment with SB216763 (2.5 mg/kg), a GSK-3beta inhibitor, had no effects on methamphetamine (METH)-induced hyperlocomotion (3 mg/kg of METH), stereotyped behavior (10 mg/kg of METH), and rewarding property (0.5 mg/kg of METH) in mice. These observations are completely different results from those of morphine-induced Straub‘s tail response (STR): pretreatment of mice with SB216763 significantly inhibited 30 mg/kg morphine-induced STR and attenuated the time of STR duration. Horizontal locomotor activity was also attenuated by SB216763.