Abstract:Objective: To investigate the effects of different doses of 3,3-iminodipropionitrile (IDPN) on Tourette Syndrome (TS) mice, with the aim of optimizing the modeling dose and establishing a stable TS model. Methods: 32 male C57BL/6J mice were randomly divided into a control group and a model group. The model group was administered IDPN and further subdivided into low-dose (300 mg/kg), medium-dose (350 mg/kg), and high-dose (400 mg/kg) groups. The control group received an equal volume of saline. Both groups underwent intraperitoneal injection for 7 days. After the modeling period, on day 0 and day 7, the mice were assessed for modeling effectiveness using stereotypy scoring, the number of head and body twitches, and open-field test. ELISA was used to detect the dopamine and TNF-α levels in mouse serum and brain tissue; HE staining was used to observe the morphology of the striatum and hippocampus tissues in mice. Results: The stereotype score showed that the mice in the middle and high-dose groups were successfully modeled. In the open field test, compared with the control group, only the high-dose group showed significant changes in behavior (P < 0.05). ELISA results showed that compared with the control group, the serum content of dopamine in the model group was significantly increased (P < 0.05), and the serum content of TNF-α in the middle and high dose groups was significantly increased (P < 0.05), and there was no significant difference in the content of dopamine and TNF-α in brain homogenate (P > 0.05). HE staining showed that the morphology of neurons and glial cells in the striatum and hippocampus of the control group was normal, while the striatum and hippocampus of the model group showed a small amount of neurodegeneration and a small amount of neuronal cell body swelling, and the striatum and hippocampus of the high-dose group had obvious lymphocyte infiltration. Conclusions: This study systematically compared the effects of different doses of IDPN on the construction of TS mouse models, and identified 400 mg/kg as the optimal modeling dose. The research provides data support for the dose study of TS mouse modeling, which has certain reference value for ensuring the smooth progress of the experiment in the early stage and helping to evaluate the therapeutic effect of subsequent drug intervention.