巴比妥类药物依赖性试验动物模型的建立  

ESTABLISHMENT OF ANIMAL MODELS FOR DRUG DEPENDENCE EVALUATION OF BABITALS

作　　者：陈素青[1] 崔艳英[1] 邱毅[1] 宁亚清[1] 黄新洁[1] 

机构地区：[1]北京大学中国药物依赖性研究所,北京100191

出　　处：《中国药物依赖性杂志》2012年第4期264-269,277,共7页Chinese Journal of Drug Dependence

摘　　要：目的:通过建立苯巴比妥躯体依赖及戊巴比妥精神依赖的动物模型,探索镇静催眠药依赖性评价的研究方法。方法:采用小鼠听源性诱导惊厥试验、大鼠戊四唑诱导惊厥试验、大鼠自然戒断试验建立苯巴比妥身体依赖性模型;采用大鼠条件性位置偏爱试验(CPP)建立戊巴比妥精神依赖性的模型。结果:(1)小鼠ig苯巴比妥30 d后停药,铃声刺激诱导惊厥反应,d1-7均有小鼠产生惊厥反应(P<0.01),体重明显降低(P<0.05,P<0.01);(2)在大鼠戊四唑诱导惊厥试验中,苯巴比妥组大鼠由戊四唑诱导的惊厥发生率为44.44%,与对照组比较差异有显著性(P<0.05);(3)大鼠ig苯巴比妥90 d自然戒断,戒断后体重明显降低(P<0.05),食量减少(P<0.01);(4)在大鼠CPP试验中,戊巴比妥钠组大鼠在伴药盒停留时间明显高于对照组(P<0.05),形成了明显的CPP效应。结獉论獉:大鼠、小鼠剂量递增ig苯巴比妥可以形成稳定的躯体依赖;大鼠ig给予戊巴比妥钠可观察到明显的强化效应,可以建立稳定的精神依赖。这些动物模型,可用于评价镇静催眠药的依赖性潜力。Objective： To establish animal models of phenobarbital physical dependence and pentobarbital psychological dependence for evaluation of dependence potential of sedative - hypnotic agents. Methods： Audiogenic seizures in mice, pentylenetetrazole （PTZ） - induced convulsion in rats, and natural withdrawal test in rats were used to develop the models of phenobarbital physical dependence. A conditioned place preference （CPP） paradigm of rats was used to develop the model of pentobarbital psychological dependence. Results ： （ 1 ） After phenobarbital was administered intragastrically for 30 days, mice lost body weight （ P 〈 0.05, P 〈 0.01 ） and experienced convulsions （ P 〈 0.01 ） induced by bell sound stimulus during one week after stopping phenobarbital; （ 2 ） The occurrence of PTZ - induced convulsions was 44.44% in the group of phenobarbital - treated rats, significantly different from that of the control group （ P 〈 0.05 ） ; （ 3 ） In the test of natural withdrawal, the rats were observed with significant body weight loss and food consumption decrease （ P 〈 0.05, P 〈 0.01 ） after phenobarbital administered intragastrically for 90 days ; （4） In the CPP test, rats spent significantly more time in the pentobarbital - paired compartment, as compared with saline - treated rats （P 〈 0. 05 ）, which demonstrated that pentobarbital could induce CPP in rats. Conclusion ：The stable physical dependence of phenobarbital can be established with phenobarbital in mice and rats, and the psychological dependence of pentobarbital can be established in rats. Those animal models are proposed to assess the dependence potential of sedative - hypnotics.

关 键 词：镇静催眠药 巴比妥 药物依赖性 动物模型 

分 类 号：R971.2[医药卫生—药品]