School of Psychology, Korea University, Seoul 02841, Republic of Korea.
Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Proc Natl Acad Sci U S A. 2024 Jun 11;121(24):e2401929121. doi: 10.1073/pnas.2401929121. Epub 2024 Jun 6.
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.
惩罚，如电击或体罚，采用物理疼痛和情绪困扰的混合方式来诱导行为改变。然而，一个通过选择性地关注情绪成分而产生行为改变，同时绕过通常由周围伤害感受器激活引起的疼痛的神经回路，尚未得到很好的研究。在这里，我们表明，通过基因沉默表达降钙素基因相关肽（CGRP）的神经元在臂旁核中的活性，阻断了由电击引起的成瘾样行为的抑制。此外，激活 CGRP 神经元不仅抑制了由刺激多巴胺神经元引起的成瘾行为，也抑制了可卡因自我给药引起的行为，而不会引起伤害感受反应。此外，在 CGRP 神经元的多个下游靶标中，CGRP 在中央杏仁核中的终末激活是有效的，模拟了细胞体刺激的结果。我们的结果表明，与传统的电击脚不同，CGRP 神经元的刺激不会激活周围伤害感受器，而是有效地抑制成瘾行为。
