OBJECTIVE: To develop a mouse model to mimic the behavioral and neurochemical changes of Tourette syndrome (TS) by 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induction and to investigate the effects of fluoxetine and haloperidol on head twitch response (HTR) induced by DOI. METHODS: 1) Preparation of mouse model of TS: Forty mice were randomly divided into experimental and control groups (n=20 each). DOI (1 mg/kg) was administered by peritoneal injection in the experimental group. The control group was injected with normal saline. The levels of dopamine (DA) and homovanillic acid (HVA), the metabolite of DA, in both groups were measured by high performance liquid chromatography and electrochemical detection. 2) Effects of fluoxetine and haloperidol on HTR: Eighty mice were randomly administered with either fluoxetine (2 mg/kg), haloperidol (0.8 mg/kg), fluoxetine + haloperidol or normal saline. DOI (1 mg/kg) was peritoneally injected 20 minutes later (acute trial) or 18-20 hrs after a 21 days injection of fluoxetine or haloperidol (chronic trial). The frequency of DOI-induced HTR was observed immediately after DOI injection. RESULTS: The levels of DA and HVA in the experimental group were significantly lower than those in the control group (DA: 45.00±11.24 ng/mg vs 58.16±14.51 ng/mg; HVA:10.54±1.86 ng/mg vs 12.82±2.66 ng/mg). In both acute and chronic trials, the frequency of DOI-induced HTR decreased significantly in mice administered with haloperidol alone or together with fluoxetine (P< 0.05), but it did not change significantly in mice administered with fluoxetine alone compared with the normal saline group.CONCLUSIONS:The levels of DA and HVA are reduced in mice with DOI-induced HTR. DOI-induced mouse mode of HTR can mimic the neurochemical and behavioral changes of TS paritially. Haloperidol can inhibit DOI-induced HTR in mice, but fluoxetine can not.