Abstract: OBJECTIVE To study the effects of sevoflurane on memory consolidation, and the role of PICK1/ERK1/2/GSK3β signaling pathway. METHODS C57BL/6J PICK1 knock-out mice were exposed to 2% sevoflurane for 3 h. The hippocampal tissues were collected for detecting the protein expressions of PICK1, ERK1/2, P-ERK1/2, GSK3β and P-GSK3β by Western blot. Primary hippocampal neurons were treated with phospho-ERK1/2 activator Honokiol or/and PICK1 inhibitor FSC231 before sevoflurane(2%, 3 h) exposure. Neurons were harvested for detection of p-GSK3β protein level. The open-field test and inhibitory avoidance task were enrolled for evaluation of motor activity and memory consolidation respectively. RESULTS The protein levels of PICK1, p-ERK1/2 and p-GSK3β were depressed in sevoflurane or PICK1 knock-out group. Compared with sevoflurane group, the expressions of p-ERK1/2 and p-GSK3β were further decreased in sevoflurane plus PICK1 knock-out group. The expression of p-GSK3β was inhibited by sevoflurane exposure, which could be improved by application of Honokiol. Moreover, the improvement of p-GSK3β by Honokiol could be reversed by further addition of FSC231. Finally, analysis of behaviour study showed that sevoflurane treatment or PICK1 knock-out did not alter the motor activity. However, sevoflurane administration inhibited memory consolidation. For the knock-out mice, the memory consolidation was further suppressed by sevoflurane exposure. CONCLUSION Sevoflurane can inhibit the memory consolidation process, and the mechanism may be related to inhibition of the PICK1/ERK1/2/GSK3β signaling pathway.