Animal Experiment And Clinical Study For Alleviating Opiate Drug Adstinence By Method Of Lesioning Brain Nucleus Of Stereotactic Surgery

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...