苯巴比妥致大鼠身体依赖性实验

A STUDY OF PHYSICAL DEPENDENCE ON SEDATIVE - HYPNOTICS

本文采用苯巴比妥掺食法，连续给药８０ｄ，造成大鼠身体依赖性模型。自然戒断后第１４ｈ，开始出现戒断症状，并逐渐加重，第１６ｈ出现震颤、抽搐等症状，第２４ｈ出现阵发自发性惊厥，部分大鼠因惊厥而死亡。第６２ｈ症状完全自然消退。与苯巴比妥等药效剂量的安定可以部分抑制戒断症状。用荧光法对大鼠脑内的单胺类递质的测定表明：５—ＨＴ、５—ＨＩＡＡ，ＮＡ和ＤＡ的含量在依赖状态或是戒断后第７２ｈ与对照组比较，无明显的差异。用放射受体法测定苯巴比妥依赖及戒断状态大鼠脑内ＧＡＢＡ的含量，结果表明：二者ＧＡＢＡ值明显地低于空白对照组，安定替代组大鼠脑内ＧＡＢＡ含量亦显著地低于对照组。

Drung -- admixed -- food(DAF) method used by Tagashira was modifiedfor producing physical dependence on phenobarbital in rats. Phenobarbital admixedwith food was given for ten weeks according to dose schedule. Spontaneous convulsionafter drug withdrawal was used as an indicator for determining the existence of physicaldependence. Results showed that the initial abstinence syndromes began at 14 hoursafter withdrawal of drug and became more severe later on. The withdrawal signs at theearly stage were an increase in excitability accompanied by perspiration, salivation, alteraion in sexuality and loss of body weight; at the final stage, animals showed severeconvulsions, mainly clonic convulsions and all of rats tested(n = 17) demonstrated positive responses. Some of rats even showed tonic convulsions and died of such pattern ofseizures. Abstinence syndromes disappeared totally after 62 hours from drug with. drawal. Animals in the control group showed no changes in behaviors. Results fromsubstitution test showed that diazepam when using the equivalent dose to that of phenobarbital(ED50 for inducing loss of righting reflex) can only partialy suppress the phenobarbital -- induced withdrawal syndromes with the convulsive rate remaining unchanged. Measure of brain monoamines by fluorospectrophotometry indicated that thebrain concentrations of NA, DA, 5 -- HT and 5 -- HIAA remained unchanged in phenobarbital dependent rats in drug withdrawal stage. Measure of GABA levels in the brainby radio -- immunoassay showed the significant decrease in this inhibitory neurotransmitter both in phenobarbital dependent rats in drug withdrawal stage. Brain GABAlevels in diazepam -- substitution test group also kept lower when compared with thosein the control group.