Activation of CGRP neurons in the parabrachial nucleus suppresses addictive behavior

• 成果类型: Article
• 署名作者: Pyeon, Gyeong Hee; Kim, Joung- Hun; Choi, June- Seek; Jo, Yong Sang; Shin, Hee- Sup
• 署名单位: Korea University; Pohang University of Science & Technology (POSTECH)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14912
• DOI: 10.1073/pnas.2401929121
• 发表日期: 2024-06-11
• 关键词: physical punishment; drug seeking; pain; CHILDREN

摘要

Punishment such as electric shock or physical discipline employs a mixture of physical pain and emotional distress to induce behavior modification. However, a neural circuit that produces behavior modification by selectively focusing the emotional component, while bypassing the pain typically induced by peripheral nociceptor activation, is not well studied. Here, we show that genetically silencing the activity of neurons expressing calcitonin gene - related peptide (CGRP) in the parabrachial nucleus blocks the suppression of addictive - like behavior induced by footshock. Furthermore, activating CGRP neurons suppresses not only addictive behavior induced by selfstimulating dopamine neurons but also behavior resulting from selfadministering cocaine, without eliciting nocifensive reactions. Moreover, among multiple downstream targets of CGRP neurons, terminal activation of CGRP in the central amygdala is effective, mimicking the results of cell body stimulation. Our results indicate that unlike conventional electric footshock, stimulation of CGRP neurons does not activate peripheral nociceptors but effectively curb addictive behavior.