Objective:To set up methamphetamine（MA） dependence rat model and assessment system,to have a systematic study change of dopamine（DA）、5-hydroxytryptamine （5-HT） and metabolites as 3,4-dihydroxyphenylacetic acid（DOPAC）、5-hydroxy-3-indoleacetic acid（5-HIAA） and homovanillic acid（HVA） in six related encephalic regions including nucleus cortex of frontal lobe（PFC）,caudate putamen, nucleus accumbens septum（NAc）,cornu ammonis（CA）,ventral tegmental area（VTA）, and substantia nigra（SN） of the dopamine innervation circuit loop in MA rats,and explore the relationship between monoamine neurotransmitter change and methamphetamine dependence mechanism.Methods:Thirty Strague-Dawley rats were randomly assigned into six experimental groups.The experimental groups was administered methamphetamine（ip） once a day with an dose of 1mg·kg^-1（n=5）,2mg·kg^-1（n=5）,10·kg^-1（n=5）,20mg·kg^-1（n=5）, 30mg·kg^-1（n=5） and 40mg·kg^-1（n=5） in 6 days.The other thirty Strague-Dawley rats were randomly assigned into control（n=5,saline） group,blank group and four experimental groups （n=20,methamphetamine）.The experimental groups was administered methamphetamine（ip） once a day with an dose of 10mg·kg^-1（n=5,in 1 week）,10mg·kg^-1（n=5,in 2 weeks）,10mg·kg^-1（n=5,in 4 weeks） and 20mg·kg^-1（n=5）.On the time to memorize the weight,to observe stereotyped behavior and do experiment of conditioned place preference（CPP） so that to estabilish rat modle of methamphetamine dependence.Simultaneous measurement of dopamine, 5-hydroxytryptamine,3.4-dihydroxyphenylacetic aicd,5-hydroxy-3-indoleacetic acid and homovanillic acid in six ralated encephalic region of methamphet- amine dependence rat by high performance liquid chromatographic analysis with fluorescence detector.Then using statistics analysis study.Results:1.According to change of weight,the stereotyped behavior and the consequence of conditioned place preference （CPP）,had set up methamphetamine dependent rat model and assessment system.2. DA concentration in MA-dependent rats in the six related encephalic regions is relatively higher,and 5-HT concentration is much lower.3.neurotransmitter changes of MA-dependent rats differ according to the doses of different groups,DA concentration of rats in the 1mg·kg^-1,and 2mg·kg^-1 group reduced,while 5-HT concentration increased;DA,DOPAC and 5-HT concentration varied in the 10mg·kg^-1 group at different time;DA and 5-HT concentration of rats in the 20mg·kg^-1 group showed no significant change.4.In the 1-week 10mg·kg^-1 group, DA and its metabolites DOPAC decreased;in the 2-week 10mg·kg^-1 group, neurotransmitter concentration in rats showed no significant change;in the 4-week 10mg·kg^-1 group,DA in rats decreased,DA metabolites DOPAC concentration increased significantly,and 5-HT concentration increased.Neurotransmitter concentration changes in the relevant encephalic regions are similar,among which PFC,NAc,caudate putamen,and hippocampus neurotransmitter concentration showed significant change,while the VTA,SN did not.Conclusion:1.To set up methamphetamine dependent rat model and assessment system.2.The overall trend of neurotransmitter changes in the six related encephalic regions of dopamine innervation circuit loop in MA rats is as follows:The concentration of DA and DOPAC decreased,while 5-HT increased.It shows that the neurotransmitter DA, DOPAC,and 5-HT involved in behavioral changes in MA-dependent rats,formation of mechanisms such as body weight changes,and the formation of MA-dependent mechanism.The effect of MA to dependent rats varies at different period.