In this presentation, we demonstrate the effects of CHIR-99021(also known as Laduviglusib), an inhibitor relatively specific for glycogen synthase kinase-3 (GSK-3), on behaviors associated with morphine withdrawal such as jumping, rearing, and head shaking. Morphine is one of the most commonly used medicines for pain relief. Moreover, morphine-induced withdrawal is clinically well known for long-term use. However, there is no established treatment for morphine withdrawal. Therefore, we focused on a possible suppression by CHIR-99021 of morphine withdrawal as well as morphine induced Straub tail reaction and thus conducted experiments using mice that were administered with morphine (10 mg/kg i.p.) or saline once daily for five consecutive days. Our data indicated that pretreatment with CHIR-99021 significantly attenuated head shaking during morphine withdrawal. However, behaviors other than head shaking observed in mice pretreated with CHIR-99021 did not differ from those observed in the vehicle injection group. In addition, the pretreatment with CHIR-99021 significantly blocked the morphine-induced Straub tail reaction. These results suggest that the GSK-3 pathway might be involved in morphine-induced positive symptoms such as Straub tail reaction and head shaking specific for morphine withdrawal.