| Substance abuse is a chronic and relapsing brain disease. It is harmful to society and has attracted international attention. It has two important characteristics:(1) compulsive abuse behavior, (2) high relapse rate. The mechanism of substance abuse and relapses is not clear. After a large number of animal experiments and imaging studies, substance abuse is thought to be related with several neuroreceptors. It caused by the change of neurons adaptability and synaptic plasticity. Many neural structures and neurotransmitters have been involved, such as dopamine system. The mid-brain system take an important role in the substance abuse, because of its ability of reward and positively reinforcement. Dopamine is one of the most important neurotransmitter in the reward system of the brain. Studies suggested that the increase of the dopamine play an important role in substance abuse. Dopamine transporter (DAT) is glycoprotein located in dopamine neurons presynaptic membrane. DAT can reuptake dopamine into the presynaptic membrane from synaptic cleft and can prohibit the effect of dopamine. The changes of density of the DAT is a reflection of dopaminergic neurons activity.The purpose of this study was to explore the influence factors of the brain SPECT imaging with 99mTc-TRODAT-1. In this study, we illustrate the influence factor of Body Mass Index (BMI) on the brain SPECT imaging. It is the first time report in our country. We also explore the changes of the brain DAT in substance abusers and the recovery of the brain DAT after a short abstinence, such as 2 weeks and 4 weeks. We have finished 31 health subjects brain imaging and 12 methamphetamine abuser brain imaging. This study is to explore the molecular mechanism of DAT in substance abuse by advancing molecular imaging technology.Part 1. The study of relationship between BMI and striatal dopamine transporter: The brain SPECT imaging with 99mTc-TRODAT-1Objective:To assess the relationship between the body mass index (BMI) and the brain dopamine transporter (DAT) and the influence of BMI on the brain SPECT imaging with 99mTc-2β-[N,N'-bis(2-mercaptotoethyl) ethylenediamino] methyl-3β-(4-chlorophenyl) tropane (99mTc-TRODAT-1).Methods:MRI and 99mTc -TRODAT-1 SPECT imaging were performed in 31 healthy volunteers (16 males,15 females). Then make the SPECT imaging three-dimensional reconstruction. according to the MRI imaging outline the right striatum (RST) and the left striatum (LST) as region of interest (ROI) on the 4 most clearly consecutive transverse slices. Take the cerebellum (CB) as the background reference area and the corresponding uptake ratios of ST/CB LST/CB and RST/CB were calculated. The correlation tests for radio-uptake ratio (ST/CB, LST/CB, RST/CB) and BMI and age were performed, Then multiple linear regression analysis using ST/CB as dependent variable and BMI and age as independent variables was performed. The date analysis use SPSS15.0.Results:The striatum imaging is symmetrical. The radiation is higher in the front area of the striatum than the back. The average uptake ratio of the total striatum, right and left striatum is 1.71±0.16,1.70±0.16 and 1.72±0.17 respectively. The average uptake ratio of the total striatum, right and left striatum is 1.74±0.18,1.71±0.19 and 1.76±0.19 in females respectively and 1.68±0.14,1.68±0.13 and 1.69±0.15 in males respectively. The uptake ratios (ST/CB, LST/CB, RST/CB) are negatively correlated with their BMI (r=-0.53, r=-0.57, r=-0.47, all P< 0.05). The striatum uptake ratio is negatively correlated with their age(r=-0.39, P< 0.05). Then multiple linear regression analysis show that the BMI is significant independent variable (β=-0.53; t=-3.36; P=0.002).Conclusion:The striatum DAT availability is decreasing with their BMI and age increasing. Females DAT availability are slightly higher than males. With regard to the striatum DAT imaging, not only the age and the gender should be taken into account, but the BMI is also an important factor that should be treated.Part 2. Decreased striatal dopamine transporters densities in methamphetamine users after a short-term abstinent:A 99mTC-TRODAT-1 SPECT study Objective:The aim of the study was to evaluate the changes of dopamine transporters(DAT) binding in methamphetamine (METH) users after a two-week or four-week period of abstinence.Methods:99mTc-TRODAT-1 SPECT imaging was performed in 5 healthy volunteers and 12 METH abusers. Among the abusers,12 abusers underwent twice imaging (0, two-week abstinence) and 6 abusers underwent three times (previously used:T1, two-week abstinence:T2, four-week abstinence:T3). Outline the right striatum (RST) and the left striatum (LST) as ROI on the 4 most clearly consecutive transverse slices. Take the cerebellum (CB) as the reference area and the specific uptake ratio (SUR) was calculated and. Values of METH abusers were compared with healthy volunteers, the values of T1, T2 and T3 compared with each other. The date analysis use SPSS 15.0.Results:The average SUR of the healthy volunteers is 3.08±0.48, (ranged from 2.59 to 3.82); Among the METH abusers, the average SUR is 2.22±0.22, (ranged from 1.80 to 2.63) in the first time,2.41±0.24(ranged from 1.90 to 2.77) after two-week abstinence and 2.66±0.22 (ranged from 2.38 to 3.03) after four-week abstinence. The SUR of METH user was significantly decreased compared with healthy volunteers. The SUR of T3 is higher than T2, T2 is higher than T1 (all P<0.05). After correlation analysis SUR was negative correlated with their METH daily dose in T1 and T2 period imaging (r=-0.305; P=0.005, r=-0.271; P=0.027); The VAS (Visual Analogue Scale) of abuser was negative correlated with the SUR of METH abuser (r=-0.374; P=0.035)Conclusions:These findings indicate that the striatal dopamine transporters densities of methamphetamine abusers decreased compared with healthy volunteers and the decreased SUR can be reversed in a short period of abstinence. |
PDF Full Text Request