Subacute Methamphetamine Intoxication In Rats' Brain Dopaminergic Toxicity

Objective:Establishing rat subacute methamphetamine intoxication model is benefical to observe the changes regarding to the rat behavior and dopaminergic toxicity in rats' brain.In addition,investigate the basis of neurobiology in the behavior change of rat subacute methamphetamine intoxication model,another purpose is to investgate injury mechanism of subcute methamphetamine dopaminergic toxicity.Methods:Subacute methamphetamine intoxication model including 90 male rats is made by intraperitoneal injection,which were randomly divided into contrast group(n=30),low dosage group(n=30)and high dosage group(n=30),killed after the last administration d1,d7,d14 respectively.Experimental group was injected,MA 10mg/kg and 20 mg/kg respectively at eight clock at night,qd×4,when the contrast group was injected the same dosage of physiological saline.Then,the author was to observe and record the results of rats' Stereotyped Behavior and Conditioned Place Preferance.Through S-P TH/DBH antibody and spectrophotofluorometer in DA,the mentioned seven brain regions were examined,including SNC,VTA,PFC,CPu,NAc,AM and Hi.The mentioned TH masculine cell and neurotic fibre were analysed by the image analysis system.At the same time,DA were examined and analysed by spectrophotofluorometer.Results:(1)Establishing subacute methamphetamine intoxication model was successful. Compared with contrast group,SB test in low and high dosage is obviously different(P＜0.05). Besides,differences were also found between low dosage and high one,with obvious difference(P＜0.05).CPP test showed that d1 was almost different from contrast group(P＜0.05), while the conditional preference time of other groups was delayed to different degrees,with no difference(P＞0.05).(2)The image analysing results in the SNC and VTA TH masculine cell:Their immunity reaction of d1 in low dosage was excessively high(P＜0.05),d7 reduces(P＜0.01),d14 nearly comes to normality with no obvious difference(P＞0.05).By contrast,TH immunity reaction masculine in high dosage reduces with obvious difference(P＜0.05),d1 begins to reduce(P＜0.05),d7 gets to the lowest level,(P＜0.01) d14 SNC and VTA masculine cell regains to different degree(P＜0.05). (3)The results of analysing rat subacute methamphetamine intoxication SNC as well as VTA masculine cell counting:Compared with relation group,low dosage d1 increases(P＜0.05),d7 reduces(P＜0.05),d14 nearly recovers.By contrast,In high dosage reduces with obvious difference(P＜0.05),d1 begins to reduce(P＜0.05),d7 gets to the lowest level,(P＜0.01) d14 SNC and VTA masculine cell regains to different degree(P＜0.05).(4)The analysing results of TH masculine Neurotic Fibre Density in the PFC,CPu,NAc,Hi and AM:Compared with relation group,low dosage d1 CPu TH masculine Neurotic Fibre Density increases(P＜0.05),d7 reduces(P＜0.05),d14 nearly recovers.The changes of TH masculine Neurotic Fibre Density reduces with obvious difference,d1 begins to reduce,d7 gets to the lowest level,d14 masculine cell regains to different degree(P＞0.05).PFC,NAc,Hi and AM was similar to CPu,but the reduction was not evident.(5)The Image Analysing results of masculine neurotic fibre in the PFC,CPu,NAc,Hi and AM: It was similar to the analysing results of the PFC,CPu,NAc,Hi and AM TH masculine Neurotic Fibre Density.(6)The results of analysing DA by SPF rat subacute methamphetamine intoxication SNC.VTA. CPu.NAc.PFC.Hi and AM:It is similar to the analysing results of the SNC.VTA.PFC,CPu,NAc,Hi and AM TH immunohistochemistry results in seven brain regions.(7)The results of Immunohistochemistry and DBH reaction were negative in all brain regions. TH Immunohistochemistry and DA content were dose dependent in different brain regions.Conclusion:1.To different degrees,the reduction and changes appear in rat SNC,VTA,PFC,CPu,Acb,Hi and AM,with dose dependent.1.1 Tt was that ethology alter was relect to TH action and the change of DA content of SNC-CPu DA passway in rat subacute methamphetamine intoxication.1.2 Tt was that emotional disturbance(CPP) was relect to TH action and the change of DA content of MLDS in rat subacute methamphetamine intoxication.1.3 Infering the drug abuse on Methamphetamine,it was proposed that drug dependence can be associated with plasticity of DA nervous system.2.The changes of TH were consistent with rat subacute methamphetamine intoxication and DA transmitter.3 Exploring and discussing the molecular biologyical mechanism of neural intoxiciton of methamphetamine:oxidization of DA;nexcitability toxicity of neurons';mutual relationship between DA and other factors.