目的 对亚氨基二丙腈(IDPN)和2,5-二甲氧-4-碘苯-2氨基丙烷(DOI)两种抽动障碍(TD)模型的行为学特征进行观察,并测定其血浆及纹状体中的多巴胺(DA)与5-羟色胺(5-HT)等神经递质水平,为更好地选择TD模型提供理论依据并揭示TD的发生机制。方法 通过SD大鼠腹腔注射IDPN和DOI分别建立IDPN和DOI抽动障碍大鼠模型,应用双盲法观察记录两模型(大鼠)的行为学变化,从运动行为、刻板行为和分类刻板行为三个方面进行评估和比较。采用酶联免疫吸附试验(ELISA)检测两种模型鼠大脑纹状体和血浆中DA与5-HT等神经递质的含量,探讨IDPN与DOI动物模型的行为学特征及机制。结果 IDPN组大鼠和DOI组大鼠的运动行为评分和刻板行为评分均高于对照组,差异具有统计学意义(P＜0.05);IDPN组大鼠的旋转、舞蹈样运动高于对照组和DOI组,DOI组大鼠的口爪运动、自咬高于对照组和IDPN组,差异均具有统计学意义(P＜0.05)。IDPN组大鼠血浆及纹状体中的DA(5.70±3.12,137.45±20.14)明显高于对照组(0.32±0.12,68.13±12.34)和DOI组(1.01±0.74,88.56±21.30),差异具有统计学意义(F=13.43~8.6,P<0.05)。DOI组大鼠纹状体中5-HT(56.83±34.72)明显低于对照组(109.14±14.05)和IDPN组(72.52±10.03),差异具有统计学意义(F=3.65,P<0.05)。结论 IDPN模型主要表现为全身性抽动,DOI模型主要以局部抽动为主。IDPN模型可能通过影响DA系统,而DOI模型则可能通过激活5-HT受体系统,从而引起大鼠出现抽动症状。
Abstract
Objective To observe the behavior and evaluate the levels of dopamine(DA) and hydroxytryptaminel(5-HT) in striatum and plasma in rat models of tic disorder(TD) induced by iminodipropionitrile(IDPN) or 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI),and provide the evidence of selecting rat models reasonably. Methods The rats of IDPN inducement were intraperitoneally injected IDPN,and the rats of DOI inducement were intraperitoneally injected DOI.The activity scale scores,stereotypy scale scores and classified stereotypy scale scores were observed and recorded by double-blind method.The levels of DA and 5-HT in striatumin and plasma of the rat models of TD induced by IDPN or DOI were observed by ELISA,and the mechanism of the rat models was discussed. Results The activity scale scores,stereotypy scale scores in the IDPN and DOI inducement groups were higher than those in the control group (P<0.05).The scores of circling and choreoathetoid movement of rat in the IDPN inducement group were higher than those in the DOI group and control group (P<0.05).The scores of paw-to-mouth movements and self-gnawing of rat in the DOI inducement group were higher than those in the IDPN group and control group (P<0.05).The DA concentrations in plasma and striatum were higher in the IDPN model group (5.70±3.12,137.45±20.14) than those in the control group(0.32±0.12,68.13±12.34)and DOI model group(1.01±0.74,88.56±21.30) (F=13.43~8.6,P<0.05).The 5-HT concentration in striatum was found to be lower in the DOI model group(56.83±34.72) compared to that in the control group(109.14±14.05) and IDPN model group(72.52±10.03)(F=3.65,P<0.05). Conclusions The generalized tics are obviously observed in the IDPN models.The partial tics are obviously observed in the DOI models.The decreasing DA concentration in striatum of the IDPN models could lead to tic disorders.The exciting 5-HT receptor of the DOI models could lead to tic disorders.
关键词
抽动障碍 /
动物模型 /
亚氨基二丙腈 /
2 /
5-二甲氧-4-碘苯-2氨基丙烷 /
行为学 /
多巴胺 /
5-羟色胺
Key words
tic disorder /
animal models /
iminodipropionitrile /
1-2,5-dimethoxy-4-iodophenyl-2-aminopropane /
praxiology /
dopamine /
hydroxytryptamine
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基金
国家自然科学基金资助项目(81101017,81371499)
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