氟西汀和氟哌啶醇对DOI诱导头部抽动的小鼠模型的作用

Roles of fluoxetine and haloperidol in mouse models of DOI-induced head twitch response

摘要:

目的：建立并评价拟抽动秽语综合征动物模型，探讨氟西汀和氟哌啶醇对该动物模型的作用。方法：将40只小鼠随机分为实验组和对照组，实验组小鼠腹腔注射DOI建立抽动秽语综合征小鼠模型，对照组注射生理盐水。应用高效液相－电化学法检测脑纹状体内多巴胺及其代谢产物高香草酸的含量。将80只小鼠随机分为4组，分别注射氟西汀、氟哌啶醇、氟西汀加氟哌啶醇和等体积生理盐水，每组取10只给药20 min后注射DOI，通过急性实验观察药物的作用；另外10只给药21 d后注射DOI，通过慢性实验观察药物的作用。结果：与对照组比，DOI诱导的头部抽动小鼠纹状体内多巴胺和高香草酸含量降低（58.16±14.51 ng/mg vs 45.00±11.24 ng/mg，12.82±2.66 ng/mg vs 10.54±1.86 ng/mg,均 P<0.05）。无论是急性实验还是慢性实验，与生理盐水组相比，预先应用氟哌啶醇的小鼠注射DOI后抽动行为显著减少（P<0.05），预先应用氟西汀的小鼠注射DOI后抽动行为无明显改变（P>0.05）。结论：DOI诱导的头部抽动小鼠脑内多巴胺神经递质含量减少，可部分模拟抽动秽语综合征病人的神经生化和行为学改变。氟哌啶醇可抑制DOI诱导的小鼠抽动行为，氟西汀无明显作用。［中国当代儿科杂志，2007，9（5）：469-472］

Abstract:

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.