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- Title
Cocaine induces locomotor sensitization through a dopamine-dependent VTA-mPFC-FrA cortico-cortical pathway in male mice.
- Authors
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
- Abstract
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.
- Subjects
COCAINE; DOPAMINERGIC neurons; COCAINE-induced disorders; COCAINE abuse; COMPULSIVE behavior; PREFRONTAL cortex; MICE
- Publication
Nature Communications, 2023, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-37045-3