影响麦司卡林诱导小鼠甩头反应的神经元类型筛选鉴定  

Neuronal type screening and identification of head twitch responses induced by mescaline

作　　者：王媛媛[1,2] 周培岚 闫海涛 苏瑞斌 WANG Yuanyuan;ZHOU Peilan;YAN Haitao;SU Ruibin(Nanjing University of Chinese Medicine,Nanjing 210023,China;Beijing Key Laboratory of Neuropsychopharmacology,State Key Laboratory of National Security Specially Needed Medicines,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]南京中医药大学,江苏南京210023 [2]军事科学院军事医学研究院国家安全特需药品全国重点实验室,神经精神药理学北京市重点实验室,北京100850

出　　处：《中国药理学与毒理学杂志》2024年第5期353-359,共7页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的 探究影响5-羟色胺(5-HT)能致幻剂麦司卡林诱导小鼠甩头反应(HTR)的神经元类型。方法 (1)成年雄性C57BL/6J小鼠随机分成正常对照组和麦司卡林(1.56,3.125,6.25,12.5,25和50 mg·kg^(-1))组,每组15只,ip给予相应药物后观察30 min内小鼠HTR次数。(2)将5-HT 2A受体(5-HT_(2A)R)基因双侧LoxP纯合子(5-HT_(2A)^(flox/flox))小鼠分别与钙调蛋白依赖性蛋白激酶Ⅱα环化重组酶阳性(CaMKⅡα^(cre/+))、小清蛋白(PV)^(cre/+)、生长抑素(SOM)^(cre/+)或血管活性肠肽(VIP)^(cre/+)小鼠杂交得到不同类型神经元的5-HT_(2A)受体条件性敲除(cKO)小鼠(5-HT_(2A)^(ΔCaMKⅡα),5-HT_(2A)^(ΔPV),5-HT_(2A)^(ΔSOM)和5-HT_(2A)^(ΔVIP)),将每类cKO小鼠随机分为正常对照组和麦司卡林12.5 mg·kg^(-1)组,每组15只,ip给予相应药物后记录30 min内小鼠HTR次数。(3)将每类5-HT_(2A)R cKO小鼠随机分为正常对照组和麦司卡林12.5 mg·kg^(-1)组,每组12只,ip给予相应药物后记录30 min内小鼠自发活动。结果 (1)与正常对照组相比,麦司卡林3.125,6.25,12.5和25 mg·kg^(-1)组小鼠HTR显著增加(P<0.05,P<0.01)。(2)不同类型神经元的5-HT_(2A)R cKO小鼠中,只有5-HT_(2A)^(ΔCaMKⅡα)小鼠正常对照组与麦司卡林12.5 mg·kg^(-1)组间HTR次数无差异,而在5-HT_(2A)^(ΔPV),5-HT_(2A)^(ΔSOM)和5-HT_(2A)^(ΔVIP)小鼠中,与正常对照组相比,麦司卡林12.5 mg·kg^(-1)组小鼠HTR均显著增加(P<0.01)。(3)所有cKO小鼠正常对照组与麦司卡林12.5 mg·kg^(-1)组间自发活动均无显著差异。结论 锥体神经元参与介导了麦司卡林对小鼠HTR的诱导作用。OBJECTIVE To investigate the types of neurons that influence the head twitch response(HTR)induced by 5-hydroxytryptaminergic(5-HTergic)psychedelic mescaline in mice.METHODS①Adult male C57BL/6J mice were randomly divided into the normal control group and mescaline(1.56,3.125,6.25,12.5,25 and 50 mg·kg^(-1))groups,with 15 mice in each group.The drugs of the corresponding groups were ip given,and the HTR frequency of mice was recorded for 30 min.②5-HT 2A receptor(5-HT_(2A)R)gene bilateral LoxP homozygous mice(5-HT_(2A)flox/flox)were hybridized with calmodulin depen-dent protein kinaseⅡαcyclization recombination enzyme positive(CaMKⅡα^(cre/+)),parvalbumin(PV)^(cre/+),somatostatin(SOM)^(cre/+)or vasoactive intestinal peptide(VIP)^(cre/+)mice to obtain 5-HT_(2A) R conditional knockout(cKO)mice(5-HT_(2A)ΔCaMKⅡα,5-HT_(2A)ΔPV,^(ΔSOM) 5-HT_(2A) and 5-HT_(2A)ΔVIP).Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg^(-1) group,with 15 mice in each group.The drugs of the corresponding groups were ip given before the HTR frequency of mice within 30 min was recorded.③Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg^(-1) group,with 12 mice in each group.After receiving the corresponding drug via ip,they were placed in a spontaneous activity test box for 30 minutes and their activity levels were recorded.RESULTS①Compared with the normal control group,mescaline 3.125,6.25,12.5 and 25 mg·kg^(-1) significantly increased the HTRs of mice(P<0.05,P<0.01).②Among the different neuronal types of 5-HT_(2A)R cKO mice,onlyΔCaMKⅡα5-HT_(2A) mice had no difference in HTR frequency between the normal control group and the mescaline 12.5 mg·kg^(-1) group.In 5-HT_(2A)ΔPV,^(ΔSOM) 5-HT_(2A) andΔVIP 5-HT_(2A) mice,the HTRs of mice in the mescaline 12.5 mg·kg^(-1) group were significantly increased(P<0.01)compared with the normal control group.③There was no difference in spontaneous activity between the normal control gro

关 键 词：麦司卡林 甩头反应 锥体神经元 5-HT_(2A)受体 

分 类 号：R971[医药卫生—药品]