Activation of CGRP neurons in the parabrachial nucleus suppresses addictive behavior

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 121; no. 24; p. e2401929121
• Main Authors: Pyeon, Gyeong Hee, Kim, Joung-Hun, Choi, June-Seek, Jo, Yong Sang
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 11.06.2024
• Subjects: Amygdala; Animals; Behavior modification; Behavior, Addictive - metabolism; Behavior, Animal - physiology; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - metabolism; Cell body; Cocaine; Cocaine - pharmacology; Dopamine; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - physiology; Drug abuse; Emotional behavior; Footshock; Male; Mice; Narcotics; Neurons; Neurons - metabolism; Neurons - physiology; Nociceptors; Pain; Pain perception; Parabrachial nucleus; Parabrachial Nucleus - metabolism; Parabrachial Nucleus - physiology; Stimulation; suppression; calcitonin gene-related peptide; dopamine; parabrachial nucleus; addiction
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2401929121

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 self-stimulating dopamine neurons but also behavior resulting from self-administering 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.