| Title | Cocaine increases quantal norepinephrine secretion through NET-dependent PKC activation in locus coeruleus neurons |
| Authors | Zhu, Feipeng Liu, Lina Li, Jie Liu, Bing Wang, Qinglong Jiao, Ruiying Xu, Yongxin Wang, Lun Sun, Suhua Sun, Xiaoxuan Younus, Muhammad Wang, Changhe Hokfelt, Tomas Zhang, Bo Gu, Howard Xu, Zhi-Qing David Zhou, Zhuan |
| Affiliation | Peking Univ, State Key Lab Membrane Biol, Beijing 100871, Peoples R China Peking Univ, Inst Mol Med, Coll Future Technol, Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China Peking Univ, McGovern Inst Brain Res, PKU IDG, Beijing 100871, Peoples R China Capital Med Univ, Core Facil Ctr, Dept Neurobiol, Beijing Key Lab Neural Regenerat & Repair, Beijing 100069, Peoples R China Capital Med Univ, Beijing Inst Brain Disorders, Core Facil Ctr, Dept Pathol, Beijing 100069, Peoples R China Karolinska Inst, Dept Neurosci, S-17171 Stockholm, Sweden Peking Univ, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China Inst Neurol & Psychiat Disorders, Shenzhen Bay Lab, Shenzhen 518132, Peoples R China Ohio State Univ, Dept Biol Chem & Pharmacol, Coll Med, Columbus, OH 43210 USA |
| Keywords | READILY RELEASABLE POOL VENTRAL TEGMENTAL AREA DOPAMINE TRANSPORTER CHROMAFFIN CELLS VESICLE POOL RAT NORADRENALINE TRANSMISSION CERULEUS REWARD |
| Issue Date | 16-Aug-2022 |
| Publisher | CELL REPORTS |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/654134 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2022.111199 |
| Indexed | SCI(E) |
| Appears in Collections: | 其他实验室 膜生物学国家重点实验室 分子医学研究所 生命科学学院 心理与认知科学学院 化学生物学与生物技术学院 å å¦ä¸ å å å·¥ç¨ å¦é ¢ |
