药物成瘾和行为成瘾形成过程中个体冲动性发展变化特征及其认知神经机制

Drug addiction is chronic recurring disease that results from prolonged effect of drugs on the brain. Early detection and prevention has been established that it is the best strategy for the drug addiction treatment. Mounting evidence showed that impulsivity can predict the severity of drug abuse, indicating impulsivity is a potential treatment target for early prevention. However, it is not clear what the development trajectories of impulsivity are as the drug dependence is spiraling upwards, and what is the alternation of impulsivity contributes to the emergence and persistence of compulsive drug seeking has not been investigated yet. In the present project, we aim to identify the relationship between the impulsivity trajectories and drug dependence combined clinic and preclinic studies. Firstly, the relationship between dynamic alternations of impulsivity and cue-induce drug craving war characterized in heroin, methamphetamine addicts and pathological gamblers after different length of drug abstinence duration, and the causal relationship between them was further examined in addicts in their initial phrase after receiving the cognitive behavioral training or transcranial magnetic stimulation intervention. Their frontostriatal neural correlates i are also to be investigated in addicts and gamblers who performing behavioral tasks to measure compulsive behavior or receiving drug-associated cues while undergoing functional magnetic resonance imaging. Lastly, rodent's model of drug addiction will be used to further explore the causal relationship between impulsivity alternations and drug dependence under strict control condition on drug exposure and abstinence duration. After characterizing the profile of compulsivity and drug seeking, the drug seeking motivation, compulsive behavior and cue-induced relapse are to examined in animals injected with different doses of anti-compulsivity drug atomoxetine when they are in their initial drug exposure or drug withdrawal periods. We apply for the in vivo calcium imaging to assess the dynamic effect by drug exposure on D1 OR D2 expressing neurons in striatum and prefrontal cortex in awaking animals. These studies will shed light on the causal relationship between the trajectories of impulsivity and emergence and persistence of compulsive drug seeking, and also provide helpful insights on early intervention of behavioral and drug addiction.

药物成瘾是一种慢性复发性脑疾病，早期识别和干预是药物成瘾防治的关键。冲动性能预测成瘾的严重程度，可能成为早期干预的重要靶点，但成瘾行为发展进程中冲动行为的动态变化特征和强迫性觅药出现之间的关系尚不明确。本项目首先研究严重程度不同的行为成瘾（病理性赌博）和药物成瘾人群在戒断后不同时期冲动行为的动态变化和线索诱发渴求之间的关系，对处于成瘾发展早期的个体进行认知行为训练和经颅磁刺激干预观察这些方法对冲动行为的影响；并采用核磁共振脑成像技术研究其前额叶-纹状体环路神经机制。然后进一步建立成瘾行为的动物模型，系统研究动物在成瘾药物暴露的不同时期，以及在成瘾早期慢性注射抗冲动药物，冲动行为的变化和强迫性觅药及复吸行为的动态关系，并通过在体清醒动物钙离子成像方法研究前额叶-纹状体环路内表达D1或D2受体的神经元活动变化规律与冲动及强迫性觅药行为变化的关系。旨在为以冲动性为靶点的成瘾行为早期干预提供依据。

成瘾是一种慢性复发性脑疾病，早期识别和干预是成瘾防治的关键。冲动性能预测成瘾的严重程度，可能成为早期干预的重要靶点，但成瘾行为发展进程中冲动行为的动态变化特征和渴求状态的关系尚不明确。本课题首先研究行为成瘾（网络游戏成瘾）和物质成瘾（甲基苯丙胺、酒精）人群在戒断后不同时期冲动行为的动态变化特征，然后通过虚拟现实技术结合主观报告、心率和脑电等生理指标客观评估成瘾线索反应性和渴求程度，并对成瘾个体进行抑制控制和正念防复吸等认知行为训练，观察这些方法对冲动行为和渴求调控的影响。结果表明，（1）在强制隔离戒毒期早期，物质成瘾者不同冲动维度分别受到吸毒量、吸毒时长、诊断评估分数三个毒品成瘾严重程度指标的不同影响；随着戒断时间的延长成瘾者不同维度的冲动行为的发展变化趋势存在一定的差异，戒断时长仅对认知冲动存在负向预测作用，即仅认知冲动水平会随戒断时间的增加而降低；冲动行为抑制能力和冒险性决策行为戒断6个月之后有一定程度的恢复。网络成瘾者与物质成瘾者具有较高的冲动特质，主要表现在情绪激发状态下容易表现出冲动行为；（2）通过虚拟现实技术，可以建立不同等级程度的虚拟环境成瘾线索，成瘾者对不同等级的线索的主观渴求报告存在程度依赖效应，皮电、心率和不同频段的脑电等生理指标可以比较好测量线索反应性和渴求程度；（3）行为抑制和正念防复吸训练对甲基苯丙胺成瘾者的抑制控制能力有一定的提高，正念防复吸训练的效果更显著。但是二者训练对线索诱发的渴求反应的抑制效果不显著，需要进一步改进和完善正念防复吸训练程序。以上研究结果表明，物质成瘾和行为成瘾者的冲动行为在戒断期随着戒断时程的延长有较明显的恢复，需要进一步研究戒断时间在3个月以内的成瘾者的冲动行为的变化特征，以便更加全面的了解冲动行为的发展变化特征。但在情绪激发状态下，物质成瘾者和行为成瘾者表现出更加明显的行为抑制问题。该研究为成瘾行为的早期识别与干预提供了新的思路和技术。