Cocaine induces locomotor sensitization through a dopamine-dependent VTA-mPFC-FrA cortico-cortical pathway in male mice.
Cocaine induces locomotor sensitization through a dopamine-dependent VTA-mPFC-FrA cortico-cortical pathway in male mice.
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DOI：
10.1038/s41467-023-37045-3
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发表时间：
2023-03-21
影响因子：
16.6
通讯作者：
Zhou, Zhuan
中科院分区：
文献类型：
--
作者：
Wang, Lun;Gao, Min;Wang, Qinglong;Sun, Liyuan;Younus, Muhammad;Ma, Sixing;Liu, Can;Shi, Li;Lu, Yang;Zhou, Bo;Sun, Suhua;Chen, Guoqing;Li, Jie;Zhang, Quanfeng;Zhu, Feipeng;Wang, Changhe;Zhou, Zhuan
作为哺乳动物大脑的中心部分，前额叶皮层（PFC）参与调节可卡因诱导的行为，包括强迫寻求和恢复。虽然PFC的功能障碍已被报告在动物和人类用户与慢性可卡因滥用，很少有人知道PFC是如何参与可卡因诱导的行为。通过使用双光子Ca 2+成像同时记录清醒雄性小鼠额叶联合皮层（FrA）中数十个完整的单个网络神经元，在这里，我们报告了系统性急性可卡因暴露降低了小鼠FrA神经活动，而化学遗传学干预阻断了可卡因诱导的运动敏化。FrA神经元的活动减退严重依赖于腹内侧前额叶皮层（vmPFC）的多巴胺转运体和多巴胺传递。多巴胺D1 R和D2 R神经元在vmPFC的投射和支配的FrA神经元，其中的操纵改变可卡因引起的活动减退的FrA和运动敏化。总之，这项工作证明了清醒小鼠中急性可卡因诱导的FrA神经元活动减退，这定义了皮质-皮质投射桥接多巴胺传递和可卡因致敏。前额叶皮层与可卡因滥用有关。在这里，作者表明，可卡因抑制清醒小鼠的额叶联合皮层（FrA），并通过多巴胺依赖性VTA-vmPFC-FrA通路诱导运动敏化。
As a central part of the mammalian brain, the prefrontal cortex (PFC) has been implicated in regulating cocaine-induced behaviors including compulsive seeking and reinstatement. Although dysfunction of the PFC has been reported in animal and human users with chronic cocaine abuse, less is known about how the PFC is involved in cocaine-induced behaviors. By using two-photon Ca2+ imaging to simultaneously record tens of intact individual networking neurons in the frontal association cortex (FrA) in awake male mice, here we report that a systematic acute cocaine exposure decreased the FrA neural activity in mice, while the chemogenetic intervention blocked the cocaine-induced locomotor sensitization. The hypoactivity of FrA neurons was critically dependent on both dopamine transporters and dopamine transmission in the ventromedial PFC (vmPFC). Both dopamine D1R and D2R neurons in the vmPFC projected to and innervated FrA neurons, the manipulation of which changed the cocaine-induced hypoactivity of the FrA and locomotor sensitization. Together, this work demonstrates acute cocaine-induced hypoactivity of FrA neurons in awake mice, which defines a cortico-cortical projection bridging dopamine transmission and cocaine sensitization. The prefrontal cortex is involved in cocaine abuse disorders. Here, the authors show that cocaine suppresses frontal association cortex (FrA) in awake mice and induces locomotor sensitization through a dopamine dependent VTA-vmPFC-FrA pathway.
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影响因子：
14.8
作者：
Jackson-Lewis, Vernice;Przedborski, Serge
通讯作者：
Przedborski, Serge
影响因子：
14.8
作者：
Garaschuk, Olga;Milos, Ruxandra-Iulia;Konnerth, Arthur
通讯作者：
Konnerth, Arthur
影响因子：
56.9
作者：
EWING, AG;BIGELOW, JC;WIGHTMAN, RM
通讯作者：
WIGHTMAN, RM
DOI：
10.1073/pnas.1004745107
发表时间：
2010-07-27
影响因子：
11.1
作者：
Hong, L. Elliot;Hodgkinson, Colin A.;Stein, Elliot A.
通讯作者：
Stein, Elliot A.
影响因子：
5.7
作者：
Kufahl, PR;Li, Z;Li, SJ
通讯作者：
Li, SJ