阿片药物依赖的神经机制---内侧前额叶与药物的心理依赖

Mental dependence, characterized by craving and impulsive seeking behavior, is the matter of intensive study in the field of drug addiction. The mesolimbic dopamine system has been suggested to play an important role in rewarding of drugs and relapse. Although chronic drug use can induce neuroadaptations of the mesolimbic system and changes of drug reinforcement, these mechanisms cannot fully account for the craving and the compulsive drug-using behavior of addicts. Acknowledging the reinforcement effects of drugs, most previous studies have studied the impact of environmental cues and conditioned learning on addiction behavior, often using established classical or operant conditioning model. These studies, however, paid little attention to the role of cognitive control and emotion in addiction. These mental factors that are believed to have an important influence on conditioned learning. The medial prefrontal cortex (mPFC) has close anatomic and functional connections with the mesolimbic dopamine system. A number of the cognitive neurological studies demonstrate that mPFC is involved in motivation, emotional regulation, monitoring of responses and other executive functions. Thus we speculated that the function of abnormality in mPFC following chronic drug use would cause related to the abnormal behavior in addicts including impulse and emotional changes. In the present study of a series of experiments, we used functional magnetic resonance imaging to examine the hemodynamic response of the mPFC and related circuits to various cognitive and emotional stimuli in heroin addicts and to explore the underlying dopamine neuromechnism by microinjection of tool drugs into the mPFC in laboratory animals. In the first experiment, we found that heroin patients, relative to the normal controls, took a much shorter time and committed more errors in completing the more demanding of cognitive regulation in the reverse condition of the task, while the neural activity in anterior cingulate cortex (ACC) was attenuated. In the second experiment, the scores of the heroin patients in self-rating depression scale (SDS) and Self-rating anxiety scale (SAS) were significantly higher than the normal controls and they rated the negative pictures more aversive than the normal controls. Being congruent with the behavioral results, hemodynamic response to negative pictures showed significant difference between the two groups in bilateral ventral mPFC (VMPFC), amygdala, and right thalamus. The VMPFC of patients showed increased activation than normal controls, whereas activation in the amygdala of patients was weaker than that in normal subjects. Our third experiment showed that microinjection of D1 receptor agonist SKF38393 into the mPFC of rats decreased hyperactivity, which was induced by morphine injection, in contrast, D1 receptor antagonist SCH23390 increased the hyperactivity, These findings suggest: (1) The behavior and neural activity in ACC of addicts changed in chronic drug users. Their impulsive behavior might result from the abnormal neural activity in the mPFC especially the ACC. (2) Heroine patients were more depress and anxiety than normal controls. The dysfunction of the mPFC---amygdala circuit of heroine addicts might be related to the abnormal emotion response. (3) Dopamine in the mPFC has an inhibitory effect on morphine induced behavior. The hyperactivity induced by chronic morphine was reduced by dopamine increase with D1 receptor agonist, confirm the first experiment that the neuroadaption of mPFC system induced by chronic morphine administration appears to be the substrate the impulse behavior of drug users.

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.

海洛因成瘾者决策障碍及其行为机制的研究----短视行为及冲动、强迫和药物在决策中的作用

Addiction can be investigated from the perspective of decision making. Addicts usually make incorrect decisions when facing drug-related cues or they are driven to drugs, resulting in repeated drug seeking and taking. The present study adopted temporal discounting as behavioral task and on the basis of the fact that heroin addicts discounted more steeply than health participants (addicts preferred to choose immediate but smaller reward, regarded as myopia) which was consistent with previous research, three questions was raised and being concentrated on in this study. The first question was whether the character of myopia would be revealed in a somewhat complicated task? We designed a card game in which the participants were tested whether they would play the trump card in order to win a trick but not the whole game. Addicts played the trump card significantly earlier than controls did, indicating they focused on immediate single trick but not the game. Moreover, the performance in the card game and temporal discounting correlated significantly, suggesting addicts would display myopic decision not only in simply task like temporal discounting but also in task more complicated and similar to daily-life decision. Secondly, the present study adopted various kinds of temporal discounting tasks. In previous research, temporal discounting gain task was usually adopted. In the present study, we also adopted temporal discounting loss task. In either gain or loss task, there are two delayed amounts. Results showed in each decision condition addicts made poorer performance compared with control but in larger amount condition, addicts actually improved their decision performance. Meanwhile, addicts did not show loss aversion due to their close discount rates in gain and loss task while for controls, the discount rates were much lower in loss task than those in gain task. Thus we demonstrated that addicts were insensitive to negative outcomes by the method of temporal discounting. Finally, we investigated three mechanisms which exerted impacts on decision making. We adopted Go/NoGo task to test impulsivity and found addicts commits more errors (higher impulsivity) than controls did. We also designed a behavioral task which could be used to test drug-related compulsive behavior on human participants. Results showed addicts produced stereotyped key-pressing behavior when presented with drug-related cues. Furthermore, it was found participants with higher impulsivity displayed poorer performance in decision making but addicts with higher compulsivity only made poorer performance in smaller amount decision and the correlation between compulsivity and decision making was relative weak. In order to investigate the role of susceptibility and effect of drugs, we adopted years of abusing heroin as the indictor and discovered addicts with longer history of heroin abusing made poorer performance in smaller amount condition than addicts with shorter history. Also, the earlier the addicts began to use drug, the worse they would do in the smaller amount decision. The results here indicated drug itself could exert impact on decision making in certain condition. The present study revealed three characters of heroin addicts from the aspect of decision making: (1) focusing upon current benefit due to they preferred to choose immediate gain and delayed loss; (2) showed no loss aversion compared with healthy participants (3) inability to inhibit inappropriate response particularly when facing drug-related cue. These characters contribute to the facts that addicts seek and take drugs repeatedly while ignoring the negative consequences caused by abusing drugs.

企业经营风险决策的组织行为学研究

This thesis has investigated the risk preferences of the Chinese company managers in kinds of simulated decision situations and their perceptions of risk concerning types of business decisions. Four studies are conducted: Study I is utility analysis. 214 company managers and 46 middle - school headmasters have responded to Utility Measurement Survey. The results indicate: (1) The risk preferences of the managers vary in the different decision situations. In most of the situations, most of the managers are risk aversion; In few situations, they are risk-seeking. (2) In some of the decision situations, there are significant differences on risk preference between business managers and school headmasters, male managers and female managers, senior managers and junior managers, managers with high qualifications and managers with low qualifications, non-state-owned firms' managers and state-owned firms' managers, medium-small sized firms' managers and large-sized firms' managers. In the other situations there aren't significant differences between them. (3) In all of the decision situations, so significant differences on risk preference are found among managers with different marriage, experience, age and education. Study II is risky decision simulation. The Risky Decision Situations Simulation Survey is administered to 82 company managers. The result indicates that firm culture, business condition, survival limit and risk preference of the superior influence the managers' risk decision-making behavior. Study III is perceptions of business decision risks. 68 company managers have filled in Decision Cases Risk Perception Inventory. The results indicate: (1) Inaccurate market analysis and prediction, instable politics and the changes of economic policy are the more risky elements to strategy decision. (2) Erroneous market analysis and prediction, appearance of new technology and the changes of market demands are the more risky elements to investment decision. (3) Poor quality control, backward technology and too large stocks are the more risky elements to production decision. (4) Shortage of development fund, wrong choice in development project and limitation of the development ability are the more risky elements to new production development decision. (5) No payment of the foreign partner's capital, the changes of national relevant policy, difficulty in marketing, too high selling prices of foreign partner's equipments are the more risky elements to joint-venture decision. (6) Unfamilarity with oneself and misjudgement in qualification of oneself are the more risky elements to personnel decision. (7) Bad market of the product, defects in product quality and the changes of consumers demands are the more risky elements to marketing decision. (8) Wrong strategy and ambiguous goals are the more risky elements to public relation decision. (9) Violation of the law, ambiguous goals and poor creation are the more risky elements to advertisement decision. (10) Deterioration of diplomatic relations, unsuitable products for foreign consumers and unfamilarity with foreign market are the more risky elements to international business decision. Study IV is structured interview. 5 company managers have answered all questions of the Interview Questionnaire. The results indicate: (1) The managers think that risks are the possible unfavourable consequences of decisions; (2) The self-ratings of the managers coordinate with the results of utility measurement; (3) The managers admit that risks always accompany bussiness decision; (4) Individual difference is found among managers on risk perception. This thesis has also pointed out the important implications of the research and discussed several further questions.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with a matrix of carbon nanotubes for the analysis of low-mass compounds in environmental samples

The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for environmental analysis has been mainly focused on qualitative analysis of high-mass molecules, such as toxins, humic acid, and microorganisms. Herein,we describe a novel MALDI-TOF-MS method with a matrix of oxidized carbon nanotubes for analysis of low-mass compounds in environmental samples. A number of chemicals in the environment were qualitatively analyzed by the present method, and it was found that most of them, especially the highly polar chemicals, were measurable with high sensitivity. With the intrinsic ability to measure high-mass chemicals, this method can compensate for the current shortage of methods for environmental analysis for the measurement of highly polar or high-mass chemicals. For sample analysis, arsenic speciation in Chinese traditional medicines was qualified and diphenylolpropane in water samples was quantified. With the relatively high tolerance of the method to interfering molecules, a simple pretreatment or even no pretreatment could be employed before MS detection. Furthermore, this method can be employed in a high-throughput format.