慢性海洛因成瘾者的冲动性和行为抑制缺陷脑机制

In recent years, the deficit of inhibition has become an important reason for explaining addiction. Response inhibition resembles the compulsive drug seeking behavior and it is the basement of addiction inhibition deficits. However, there were no enough evidence for the relationship between addiction and response inhibition deficits and the results of the neuro mechanisms studies remains unclear. Few studies has focused on the exploring the heroin users. Among those paradigms for study response inhibition deficits, stop signal is a very suitable model for the representation of compulsive drug seeking, but only a few researches has worked on this paradigm. In this study, we selected about 100 heroin abusers and had behaviour and neuro imaging scannings for investigating the response inhibition deficits. The behaviour researches found: first, the chronic heroin users had longer reaction time than control group and this reaction time were not affected by stop signals in heroin users. Second, heroin users had less waiting time than control group and they were more impulsive but less flexibility. Their erro monitoring and flexibale adjustment ability decreased. Third, the SSRT of heroin users was significantly longer than control group. These results suggested that the inhibition of heroin users were impaired. Further investigation showed that the SSRT of heroin users had positive correlation of four factor scores of ASI and the macro correlation coefficient was factor three of drug use. This correlation suggested that drug use was the main reason of inhibition deficits. fMRI results mainly focused on the ANOVA analysis for group difference. First, there was no intensity difference in M1 and SMA brain areas between the two groups. Second, heroin users had less activation in right dorsalateral prefrontal cortex, right inferior prefrontal cortex and anterior cingulated cortex, while in bilateral striatum and amygdala, heroin users had more activation than control group. The right prefrontal cortex was indentified as the main inhibition brain area. The anterior cingulated cortex has relationship with erro monitoring and amygdale was an important brain area for impulsivity and emotion control. The network of these brain areas was envovled in impulsivity and inhibition and it was suggested the mainly damaged network for heroin users’ disinhibition. We also investigated the gray matter changes of heroin users and found that chonic heroin use made their gray matter density decreased in prefrontal cortex (including bilateral dorsalateral prefrontal cortex, obital frontal cortex, inferior prefrontal cortex) and anterior cingulated cortex. The gray matter density in these brain regions had negative correlation with drug use duration. In conclusion, we indentified the disinhibition of heroin users and its neuro mechanism. Their compulsivity brain areas had more activation than control group and their inhibition brain areas had less activation than normal control. On the other side, the biological mechanism of this activation changes was the gray matter density decrease in these brain areas.

Development of an in vitro multicellular tumor spheroid model using microencapsulation and its application in anticancer drug screening and testing

In this study, an in vitro multicellular tumor spheroid model was developed using microencapsulation, and the feasibility of using the microencapsulated. multicellular tumor spheroid (MMTS) to test the effect of chemotherapeutic drugs was investigated. Human MCF-7 breast cancer cells were encapsulated in alginate-poly-L-lysine-alginate (APA) microcapsules, and a single multicellular spheroid 150 mu m in diameter was formed in the microcapsule after 5 days of cultivation. The cell morphology, proliferation, and viability of the MMTS were characterized using phase contrast microscopy, BrdU-Iabeling, MTT stain, calcein AM/ED-2 stain, and H&E stain. It demonstrated that the MMTS was viable and that the proliferating cells were mainly localized to the periphery of the cell spheroid and the apoptotic cells were in the core. The MCF-7 MMTS was treated with mitomycin C (MC) at a concentration of 0.1, 1, or 10 times that of peak plasma concentration (ppc) for up to 72 h. The cytotoxicity was demonstrated. clearly by the reduction in cell spheroid size and the decrease in cell viability. The MMTS was further used to screen the anticancer effect of chemotherapeutic drugs, treated with MC, adriamycin (ADM) and 5-fluorouracil (5-FU) at concentrations of 0.1, 1, and 10 ppc for 24, 48, and 72 h. MCF-7 monolayer culture was used as control. Similar to monolayer culture, the cell viability of MMTS was reduced after treatment with anticancer drugs. However, the inhibition rate of cell viability in MMTS was much lower than that in monolayer culture. The MMTS was more resistant to anticancer drugs than monolayer culture. The inhibition rates of cell viability were 68.1%, 45.1%, and 46.8% in MMTS and 95.1%, 86.8%, and 91.6% in monolayer culture treated with MC, ADM, and 5-FU at 10 ppc for 72 h, respectively. MC showed the strongest cytotoxicity in both MMTS and monolayer, followed by 5-FU and ADM. It demonstrated that the MMTS has the potential to be a rapid and valid in vitro model to screen chemotherapeutic drugs with a feature to mimic in vivo three-dimensional (3-D) cell growth pattern.