期刊
CELL REPORTS
卷 40, 期 7, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2022.111199
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资金
- National Key Research and Development Program of China [2016YFA0500401]
- National Natural Science Foundation of China [31930061, 21790394, 31761133016, 31821091, 82022018, 32070958, 82161138025, 82101568]
- Beijing Municipal Science and Technology Commission [Z181100001518001]
- NIH/NIDA
- Shenzhen-Hong Kong Institute of Brain Sci-ence [2019SHIBS0004]
- Post-doctoral Fellowship of Peking-Tsinghua Center for Life Sciences
This study demonstrates that cocaine directly increases the frequency of quantal NE release through regulation of NET and downstream PKC signaling, which modulates the activity of LC-NE neurons and cocaine-induced stimulant behavior.
The norepinephrine neurons in locus coeruleus (LC-NE neurons) are essential for sleep arousal, pain sensa-tion, and cocaine addiction. According to previous studies, cocaine increases NE overflow (the profile of extracellular NE level in response to stimulation) by blocking the NE reuptake. NE overflow is determined by NE release via exocytosis and reuptake through NE transporter (NET). However, whether cocaine directly affects vesicular NE release has not been directly tested. By recording quantal NE release from LC-NE neu-rons, we report that cocaine directly increases the frequency of quantal NE release through regulation of NET and downstream protein kinase C (PKC) signaling, and this facilitation of NE release modulates the activity of LC-NE neurons and cocaine-induced stimulant behavior. Thus, these findings expand the repertoire of mech-anisms underlying the effects of cocaine on NE (pro-release and anti-reuptake), demonstrate NET as a release enhancer in LC-NE neurons, and provide potential sites for treatment of cocaine addiction.
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