目的 观察亚氨基二丙腈(iminodipropionitrile,IDPN)和2,5-二甲氧-4-碘苯-2-氨基丙烷(±-1-2,5-dimethoxy-4-iodophenyl-2-aminopropane,DOI)诱导的抽动障碍(tic disorder,TD)动物模型的运动抽动和刻板行为表现,为选择可以更好地模拟TD特征性行为的造模方法提供依据。方法 SD大鼠30只随机分3组,每组10只。IDPN组大鼠给予IDPN 150 mg/kg腹腔注射,连续7 d,DOI组大鼠给予DOI 1 mg/kg腹腔注射,连续15 d,正常组给予生理盐水腹腔注射,连续7 d,给药体积均为1 mL/100 g。造模结束后记录各组大鼠在造模结束第1至第7天、第14天和第28天的运动行为评分、刻板行为评分和分类刻板行为评分。结果 IDPN组和DOI组大鼠在第1至第4天的运动评分、刻板行为评分,除理毛、舔咬笼子以外的分类刻板行为评分均高于正常组,且IDPN组大鼠在第5、6、7、14、21、28天的运动评分和第5、7、14、21、28天的刻板行为评分均高于正常组和DOI组,差异均有统计学意义(P<0.05)。IDPN组大鼠的吃木屑、旋转、摆头、舞蹈样运动等分类刻板运动评分均高于DOI组,DOI组大鼠口爪运动、自咬等分类刻板运动评分均高于IDPN组,差异均有统计学意义(P<0.05)。结论 IDPN模型与DOI模型均可以模拟抽动患者的兴奋性增高,活动增多和抽动等症状,表观效度较好。与DOI模型相比较,IDPN模型具有建模时间短,模型维持时间长久,且花费较少等优势。
Abstract
Objective To observe the tic and stereotypy 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 fully reflecting the characteristic behavior change. Methods A total of 30 SD rats were randomly divided into 3 groups,IDPN inducement group,DOI inducement group and control group(n=10).The rats in the IDPN inducement group were intraperitoneally injected 150 mg/kg IDPN,and the treatment were given daily for a consecutive 7 d;those in the DOI inducement group were intraperitoneally injected 1 mg/kg DOI,and the treatment were given daily for a consecutive 15 d;those in the control group were intraperitoneally injected saline,and the treatment were given daily for a consecutive 7 d;the dosing volume was 1 mL/100g.The activity scale scores,stereotypy scale scores and classified stereotypy scale scores were observed and recorded at 1~7 d,14 d,28 d after the successful model making. Results The activity scale scores,stereotypy scale scores in the IDPN and DOI inducement groups were higher than those in the control group at 1~4 d,and all classified stereotypy scale scores except grooming and cage licking in the IDPN and DOI inducement groups were higher than those in the control group (P<0.05).The activity scale scores of rat in the IDPN inducement group were higher than those in the control group and DOI group at 5~7 d,14 d,21 d and 28 d; the stereotypy scale scores of rat in the IDPN inducement group were higher than those in the control group and DOI group at 5 d,7 d,14 d,21 d and 28 d(P<0.05).The classified stereotypy scale scores of wood chip eating,circling,head shaking and choreoathetoid movement of rat in the IDPN inducement group were higher than those in the DOI group;the classified stereotypy scale scores of repetitive paw-to-mouth movements and self-gnawing of rat in the DOI inducement group were higher than those in the IDPN group(P<0.05). Conclusions The IDPN models and DOI models can perfectly copy the high excitement,high activity and tic behavior of TD patients.The behavioral changes of TD models induced by IDPN are more obvious and longer persistence than those of the models induced by DOI.
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
Key words
tic disorders /
animal models /
iminodipropionitrile /
(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane /
praxiology
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Liu X,Wang X,Li L,et al.Influence of mesenchymal stem cell transplantation on stereotypic behavior and dopamine levels in rats with Tourette syndrome[J].PLoS One,2013,26,8(4):e62198.
[2] Huys D,Hardenacke K,Poppe P,et al.Update on the role of antipsychotics in the treatment of Tourette syndrome[J].Neuropsychiatr Dis Treat,2012,8(2):95-104.
[3] Bronfeld M,Israelashvili M,Bar-Gad I.Pharmacological animal models of Tourette syndrome[J].Neurosci Biobehav Rev,2013,37(6):1101-1119.
[4] 卫利,王素梅,崔霞,等.多发性抽动症动物模型的比较与评价[J].中华行为医学与脑科学杂志,2012,21(2):187-189.
[5] Canal CE,Morgan D.Head-switch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine:a comprehensive history,a re-evaluation of mechanisms,and its utility as a model[J].Drug Test Anal,2012,4(7-8):556-576.
[6] Diamond BI,Reyes MG,Borison R.A new animal model for Tourette Syndrome[J].Adv Neurol,1982,35(2):221-225.
[7] Al Kadasah S,Al Mutairy A,Siddiquei M,et al.Pentoxifylline attenuates iminodipropionitrile-induced behavioral abnomalities in rats[J].Behav Pharmacol,2009,20(4):356-360.
[8] Macrì S,Proietti Onori M,Laviola G.Theoretical and practical considerations behind the use of laboratory animals for the study of Tourette syndrome[J].Neurosci Biobehav Rev,2013,37(6):1085-1100.
[9] Felling RJ,Singer HS.Neurobiology of tourette syndrome:current status and need for further investigation[J].Neurosci,2011,31(35):12387-12395.
[10] Soler-Martín C,Vilardosa U,Saldaa-Ruíz S,et al.Loss of neurofilaments in-the neuromuscular junction in-a rat model of proximal axonopathy[J].Neuropathol Appl Neurobiol,2012,38(1):61-71.
[11] Khan-HA.N-nitro-L-arginine,a nitric oxide synthase-inhibitor,aggravates iminodipropionitrile-induced-neurobehavioral and vestibular toxicities in rats[J].Exp Toxicol Pathol,2012,64(7-8):791-796.
[12] Llorens J,Soler-Martín C,Cutillas B,et al.Nervous and vestibular toxicities of acrylonitrile and iminodipropionitrile[J].Toxicol Sci,2009,110(1):244-245.
[13] Boadas-Vaello P,Riera J,Llorens J.Behavioral and pathological effects in the rat define two groups of neurotoxic nitriles[J].Toxicol Sci,2005,88(2):456-466.
[14] Canal CE,Booth RG,Morgan D.Support for 5-HT2C receptor functional selectivity in vivo utilizing structurally diverse,selective 5-HT2C receptor ligands and the 2,5-dimethoxy-4-iodoamphetamine-elicitedhead-twitch response model[J].Neuropharmacology,2013,70(7):112-121.
[15] Schindler EA,Dave KD,Smolock EM,et al.Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide(LSD)[J].Pharmacol Biochem Behav,2012,101(1):69-76.
[16] Bronfeld M,Bar-Gad I.Tic disorders:what happens in the basal ganglia[J].Neuroscientist,2013,19(1):101-108.
[17] 阮铭,吴敏,马碧涛.抽动障碍大鼠模型的建立与选择[J].中华神经医学杂志,2012,11(9):873-875.
基金
国家自然科学基金资助项目(81101017)