青少年吸毒对脑功能损害的研究停留在毒品的短期效应水平。前额皮质内侧部(Medial prefrontal cortex，mPFC)是毒品作用的重要靶点。锥体神经元(Pyramidal neuron，PN)是mPFC中主要投射神经元，其输出活动受兴奋和抑制(Excitation-Inhibition，E-I)输入的整合调控。E-I失衡引起脑功能异常。γ-氨基丁酸能中间神经元（γ-Aminobutyric acidergic interneuron, GABA IN）是PN抑制输入的主要来源。本项目拟采用行为、形态、光遗传、分子生物和电生理等手段，探究青春期可卡因滥用对mPFC中GABA IN—PN突触传递路径发育和功能的长期影响；观察GABA IN—PN突触传递路径的可塑性变化，对成年时出现的病理行为的调控作用和机制。本项目研究结果将有助于为针对青少年吸毒患者的戒毒新药开发提供思路和方向

Adolescence marks an important developmental period of neurobiological change. Drug abuse in adolescence may influence the development and function of brain as well as physical and psychological health, which contribute to later heightened vulnerability to develop mental disorders in adulthood, such as drug addiction, depression and cognitive disorder. Lots of studies began to explore the neurobiology of adolescent drug abuse. However, most of them focus on the short-term effects of abused drug exposure in adolescence on the development of brain. The medial prefrontal cortex (mPFC) is an important neural substrate for the development of drug addiction. Pyramidal neurons (PN) in mPFC project to several brain area, such as amygdale, ventral tegmental area, nucleus accumbens, hippocampus and dorsal striatum, and is involved in higher cognitive functions, such as reward, decision making, working memory and impulsive control. The output activity of PN is under the integrated control of excitatory and inhibitory (E-I) inputs. Imbalance of E-I control of PN lead to neurological disorders. The inhibitory inputs to PN are mainly from local γ-Aminobutyric acid (GABA) interneuron (IN) in mPFC. The aims of this study are : (1)Test the long-term effects of adolescent cocaine exposure on the structure and function of GABA IN—PN inhibitory synaptic circuit of mPFC in adulthood; (2)Examine the role of these adaptations of GABA IN—PN inhibitory synaptic circuit in later cocaine-related addiction behavior in adults; (3)Explore the molecular mechanism underlying these adaptations of GABA-IN—PN synaptic circuit in adult rats who have an adolescent cocaine exposure history. This study will contribute to better understand the neurobiology of drug addiction and will facilitate advances in prevention and treatment during adolescence.