Abstract: Objective To investigate the effect and mechanism of gastrodin on head twitch behavior in rats with Tourette syndrome (TS). Methods 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induction method was used to replicate TS rat model. Forty Wistar rats were randomly divided into four groups (n=10): the normal group (gastric administration of normal saline), the TS model group (from the first day of modeling, intragastric administration with normal saline at 2 h after DOI injection), the TS+ gastrodin group (from the first day of modeling, intragastric administration with 30 mg/kg gastrodin at 2 h after DOI injection), and the TS+gastrodin+CHIR-99021 group [glycogen synthase kinase-3β (GSK- 3β) inhibitor] (from the first day of modeling, 2 h after DOI injection, intraperitoneal injection with 2 mg/kg CHIR-99021 firstly, and then intragastric administration with 30 mg/kg gastrodin), continuous administration for 21 d. After the last administration, the rat’s head twitching behavior within 30 min was counted. The levels of striatal 5-hydroxyindole (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and dopamine (DA) were detected by kits. The number of DA neurons in the substantia nigra was detected by immunohistochemical method. The expression of 5-HT transporter (SERT), 5- hydroxyindole 2A receptor (5-HT2AR), 5-hydroxyindole 2C receptor (5-HT2CR) and GSK-3β phosphorylation in the striatum were detected by Western blot assay. Results Compared with the normal group, the number of head twitches, DA level, number of DA neurons, SERT level and p-S9-GSK-3β, p-S9-GSK-3β/t-GSK-3β level increased in the TS model group, and the 5-HT level decreased (P＜0.05). Compared with the TS model group, the number of head twitches, DA level, number of DA neurons, SERT level and p-S9-GSK-3β, p-S9-GSK-3β/t-GSK-3β level decreased in the TS+gastrodin group, and the 5-HT level increased (P＜0.05). Compared with the TS+gastrodin group, the number of head twitches, DA level, number of DA neurons, SERT level and p-S9-GSK-3β, p-S9-GSK-3β/t-GSK-3β level increased , and the 5-HT level decreased in the TS+gastrodin+CHIR-99021 group (P＜0.05). Conclusion Gastrodin can improve the head twitch behavior of TS rats, and its mechanism may be by inhibiting the phosphorylation of GSK-3β, regulating the expression of SERT, affecting the level of 5-HT, and then inhibiting the release of DA in striatum.

Key words: gastrodin, glycogen synthase kinase 3 beta, serotonin, dopamine, receptor, serotonin, 5-HT2A, receptor, serotonin, 5-HT2C, Tourette syndrome, 5-hydroxytryptamine transporter