多动症是一个普遍的儿童行为异常疾病，其特征为持续的注意缺陷，多动和冲动。多动症有认知、情感和社会功能损害现象。多巴胺系统异常在多动症的发病中起关键作用。我们发现多动症转基因小鼠存在模式完成障碍且氟哌啶醇对此具有解救作用。研究表明，多动症的发病和环境因素关系密切，其中包括母孕期肥胖。我们发现母孕期肥胖引起后代的逆转学习异常，但后代的血清指标正常，提示中枢系统功能和结构的异常可能早于代谢系统。同时，我们发现母孕期肥胖显著改变纹状体多巴胺内稳态及瘦素信号系统。.目前普遍认为多巴胺系统参与成瘾和习惯化建立，但调节机制不清。在多巴胺神经元特异性敲除NMDAR的小鼠模型上，我们发现降低多巴胺能神经元NMAR表达可减弱尼古丁成瘾，该发现从细胞水平为控烟治疗提供了高特异性的分子靶点。我们首次揭示多巴胺能神经元中的NMDAR参与调控习惯化学习。综上所述，多巴胺系统的异常和多动症的认知功能障碍关系紧密，通过多动症相关的动物模型的研究，无疑将为理解及治疗多动症提供十分有益的线索。

ADHD (attention-de？cit/hyperactivity disorder) which is characterized by hyperactivity, impaired sustained attention, impulsivity and distractibility, is a common behavior disorder for children, with cognition, emotion and social function deficit. Dopamine system disorder is critical for the pathogenesis of ADHD. We found DAT +/- (dopamine transporter) mice existed pattern completion deficit, which was rescued by haloperidol. The ADHD is closely related with environment factors, including maternal obesity. In our study, pregnant obesity impaired reversal learning, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defect possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. .At present, dopamine system is considered involving in the addition and habit but the mechanism remains unclear. We found that mice with dopaminergic neuron-specific NMDAR1 deletion are impaired in nicotine addiction, which might provide a high affinity cellular target for nicotine control in cellular level. Besides, we found that NMDA receptors in dopamine neuron involved in habit-learning. In conclusion, it will help to understand and treat the ADHA by ADHD-related animal model studies for dopamine system abnormality place important role in the impaired cognition of ADHD.

多动症是一个普遍的儿童行为异常疾病，其特征为持续的注意缺陷，多动和冲动。多动症有认知、情感和社会功能损害现象。多巴胺系统异常在多动症的发病中起关键作用。我们发现多动症转基因小鼠存在模式完成障碍且氟哌啶醇对此具有解救作用。研究表明，多动症的发病和环境因素关系密切，其中包括母孕期肥胖。我们发现母孕期肥胖引起后代的逆转学习异常，但后代的血清指标正常，提示中枢系统功能和结构的异常可能早于代谢系统。同时，我们发现母孕期肥胖显著改变纹状体多巴胺内稳态及瘦素信号系统。目前普遍认为多巴胺系统参与成瘾和习惯化建立，但调节机制不清。在多巴胺神经元特异性敲除NMDAR的小鼠模型上，我们发现降低多巴胺能神经元NMAR表达可减弱尼古丁成瘾，该发现从细胞水平为控烟治疗提供了高特异性的分子靶点。我们首次揭示多巴胺能神经元中的NMDAR参与调控习惯化学习。综上所述，多巴胺系统的异常和多动症的认知功能障碍关系紧密，通过多动症相关的动物模型的研究，无疑将为理解及治疗多动症提供十分有益的线索。