摘要
目的:
本研究旨在探讨应用定向手术毁损与阿片类药物产生心理(精神)依赖密切相关的脑内关键核团,阻断中脑-边缘多巴胺系统环路,缓解、消除药物的心理(精神)依赖,控制、降低脱毒后的复吸率,从而达到彻底戒除毒瘾,为临床戒毒提供一种新颖的、全面彻底的、安全有效的新方法。
方法:
本研究包括动物实验和临床研究两部分。
1.动物实验:
以大鼠为实验动物,以条件性地点偏爱实验为观察方法,比较毁损伏隔核、腹侧苍白球对动物觅药行为的作用,有无并发症发生,筛选出更适合应用于临床戒毒治疗的脑内毁损靶点。
(1)制作条件性地点偏爱实验箱,A侧为注射吗啡侧;
(2)40只大鼠随机平分为伏隔核毁损组和腹侧苍白球毁损组,每组又分为成瘾组和对照组;
(3)按逐日递增原则,在实验箱A侧向大鼠腹腔注射盐酸吗啡,通过戒断症状评分标准进行行为学评估,确定大鼠成瘾以及对实验箱A侧的偏爱(观察记录15min,900s大鼠在A、B两侧停留的平均时间);
第四军二大学博士学位论文
N)定向手术毁损伏隔核、腹侧苍白球;
6)术后再次行条件性地点偏爱实验,记录、比较术前、
术后大鼠在实验箱A侧停留的平均时间,并与对照组(假
手术组)比较,观察手术对大鼠觅药行为的改变作用,
有无副作用及并发症发生;
L 临床研究:
根据动物实验的结果,在查阅文献、咨询专家、走访同
行、社会调查、学科论证的基础上,临床收治24例吸毒患
者行双侧伏隔核毁损术。
门)制定手术适应症标准:
吸毒史三年以上;
药物戒毒3次以上,脱毒后3周内发生复吸;
患者、家属自愿要求;
无手术禁忌。
u)制定疗效标准:
优:术后半年以上无复吸意念及行为;
良:术后半年内偶有复吸意念及行为,但较术前明显
减轻:
差:术后半年内发生复吸,毒癌发作程度基本同术前。
臼)规范治疗程序:
药物脱毒(依赖性药物,非依赖性药物);
尿检、纳络酮催瘤试验结果阴性;
作者 王学廉 第5页2002A5.07
第四军巴大学博士学位论文
手术:采用CRW立体定向仪,Philip螺旋CT薄层扫
描(层厚 3mm,层距 ZnunX 伏隔核(accUmbens
nucleus)坐标:参照 SchaltembrandEailey人脑图谱,
ACqC线下 8-10nun,撇原点(MP)前侣-22nun,中
线旁开 41 onun,以伏隔核的核心部*ore)做为原
始靶点。刺激频率及阈值:100HZ,6七;RadioniC
射频治疗仪;射频电极:1.smm;毁损温度85℃,时
间60s,每侧间隔3-4mm各毁损两个针道,每个针道
间隔1共毁损6个层面。
N)制定手术疗效及安全性观察评价指标:
尿检;
纳络酮催瘤实验;
血、尿、唾液、毛发中吗啡含量检测;
药物依赖诊断量表u*IDoD):
心理学调查量表:
艾森克人格问卷oPQ)。
明尼苏达多相人格调查表(MNQI):
卡特尔十六种个性因素测查表门6N):
药物心理依赖调查量表(自编人
(5)118th:
不定期随机抽查;
随访形式:家庭访问(面对面),门诊预约(面对面),
电话,邮寄填写随访调查表;
作者 王学廉 第6页22265.07
第四军区大学博士学位论文
随访期 0.5—22个月,平均随访期 13个月。
结果:
1.动物实验
门)在毁损伏隔核组中,经统计学分析,术前成瘤组大鼠
在A、B两侧各停留的平均时间与术前对照组大鼠在A、B两
侧各停留的平均时间相比,P<0刀1,差异显著,有统计学意义,
表明术前成癌组大鼠对A侧有?
Objective:
Opiate drug dependence is a very serious medical and social problem.Drug dependence includes two aspects:physical dependence and psychic dependence/Though there has been a much progress of neuroscience in studying drug dependence and effective measures in controlling abstinence syndrome for many years,high relapse rate after detoxification due to intractable psychic dependence is still universally acknowledged as a difficult problem.At present,because of uncontrolling psychic dependence,treating drug dependence clinically is in a situation of detoxificating easily but de-addict difficultly.Correlation between psychological dependence and nerve nuclus <. neuro-circuu\ neuro-transmitter has been the focus of much recent investigation.Plenty of animal experiment results confirmed that there is an intimate relation between psychological dependence and mesocorticolimbic dopamine system.Both nucleus accumbens and ventral pallidum is the most important nuclus in the mesocorticolimbic dopamine system which play a very crucial role in drug-induced psychological dependence.Lesions made by surgical or chemical method in nucleus accumbens or ventral pallidum can change animals' drug-seeking behavior.But at present,making a lesion in nerve nuclus by stereotactic surgery to treat drug-induced psychological dependence is much more limited to animal experiments.No reports of using stereotactic surgery to deal with drug abstinence in human beings be recorded or published.
The objective of this study is to explore making a lesion in nerve nuclus which have intimate relation with drug-induced psychological dependence by stereotactic surgery,blocking mesocorticolimbic dopamine circuit, alleviating or getting rid of craving for drugs,lowering relapse rate after detoxification and developing a new,complete,safe and effectiveness therapy of drug abstinence.
Methods:
The study includes two parts:animal experiment and clinical study. lAnimal experiment:
40 male SD rats were used as animal models.A case of conditioned place preference.was made and A side was paired with injection morphine.Electrolytic lesions of the nucleus accumbens and ventral pallidum was done separately in 20 rats and changes of drug-seeking behavior was observed by conditioned place preference.Each group of rats again divided into morphine dependence group and controlling group.Recording and comparing mean time of rat staying in A side pre-operation and post-operation to screen out which nucleus is safer and more effectively lesioned in human beings by stereotactic surgery .Side effects and complications were also observed.
2.Clinical study:
On the basis of animal experiment,we did 24 cases of stereotactic surgery making a lesion in nucleus accumbens bilaterally to treat opiate drug dependence. Indications, criterion of therapeutical effect,treatment process, therapeutical and safe evaluation index of the surgery were formulated particularly.
(1) Indications criterion:
drug-taking history is more than 3 years, detoxification is more than 3 times,
relapse occurred within 3 weeks after each time of detoxification, patients underwent the operation of their own free will, no contraindications.
(2) Criterion of therapeutical effect:
excellent: relapse ideas and behavior not occurred over half of a year after surgery;
good: relapse ideas and behavior occurred occasionally within half of a year after surgery, but the withdrawal symptoms was obviously alleviated than that of pre-operation;
poor: relapse occurred within half a year after surgery and the withdrawal symptoms were as well as that of pre-operation;
(3) Treatment process:
(D patients should be treated by medication for detoxification; ?results of drug urinalysis and naloxone test was negative; (? the operation could be done.
(4) Therapeutical and safe evaluation index of the surgery:
(1) drug urinalysis;
(2) naloxone test;
(3) drug testing in blood,urine,saliva and hair,
(4) schedule of clinical interview for diagnosis of drug dep
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