Cocaine increases quantal norepinephrine secretion through NET-dependent PKC activation in locus coeruleus neurons

Autor: Feipeng Zhu, Lina Liu, Jie Li, Bing Liu, Qinglong Wang, Ruiying Jiao, Yongxin Xu, Lun Wang, Suhua Sun, Xiaoxuan Sun, Muhammad Younus, Changhe Wang, Tomas Hokfelt, Bo Zhang, Howard Gu, Zhi-Qing David Xu, Zhuan Zhou
Rok vydání: 2022
Předmět:
Zdroj: Cell Reports. 40:111199
ISSN: 2211-1247
Popis: The norepinephrine neurons in locus coeruleus (LC-NE neurons) are essential for sleep arousal, pain sensation, 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 neurons, 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 mechanisms 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.
Databáze: OpenAIRE