华中科技大学李熳等研究人员合作揭示大麻素1型受体，在mPFC谷氨酸能和GABA能神经元上对瘙痒感觉和情绪的差异性调控。相关论文于2024年12月11日在线发表在《中国药理学报》杂志上。

研究人员探讨了大麻素1型受体（CB1R）如何通过调控中前额叶皮层（mPFC）中谷氨酸能和GABA能神经元的活动，差异性地调节瘙痒感觉和情绪。研究人员建立了氯喹（CQ）引起的急性瘙痒和卡替泊醇（MC903）引起的慢性瘙痒模型。研究人员使用光纤钙成像技术检测了两种神经元对瘙痒的反应活动。CB1R拮抗剂AM251（0.5 mg，200 nL）通过植入的导管微注射到mPFC。

研究表明，化学遗传学激活mPFC中的谷氨酸能神经元并抑制GABA能神经元可以减少抓挠行为和慢性瘙痒引起的焦虑。GABA能神经元而非谷氨酸能神经元参与急性瘙痒引起的厌恶反应。CB1R在谷氨酸能和GABA能神经元上的作用方式不同，调节慢性瘙痒引起的抓挠和焦虑。然而，CB1R不影响急性瘙痒引起的抓挠。CB1R在GABA能神经元上的作用调节急性瘙痒引起的厌恶反应，而在谷氨酸能神经元上则没有此效应。这些结果可能为开发针对CB1R的治疗策略提供指导，以应对瘙痒引起的感觉和情绪反应。

据了解，瘙痒引起强烈的抓挠欲望，并诱发负面情绪，如厌恶和焦虑。抗组胺药物是临床上管理瘙痒的关键，但它们在控制中度和重度瘙痒方面的治疗效果仍然有限。大脑中处理瘙痒及瘙痒引起的厌恶和焦虑的神经回路至今尚不清楚。人类脑成像研究表明，mPFC参与瘙痒的情感和动机成分的处理。

附：英文原文

Title: Differential regulation of pruritic sensation and emotion by cannabinoid type 1 receptors on mPFC glutamatergic and GABAergic neurons

Author: Zhanmu, Ou-Yang, Yang, Yang, Feng, Bin, Wang, Hong-yang, Li, Hao, Zhou, Hui-juan, Ge, Wen-qiang, Wan, Ke-xing, Wang, Sui-xi, Zhang, Kai-ling, Zhang, Hong, Pei, Lei, Pan, Hui-lin, Tian, Qing, Li, Man

Issue&Volume: 2024-12-11

Abstract: Itch causes a strong urge to scratch and induces negative emotions, such as aversion and anxiety. Antihistamine medications are key in the clinical management of pruritus, but their therapeutic efficacy in controlling moderate and severe itching remains limited. The neural circuits in the brain that process itching and itch-induced aversion and anxiety remain unclear so far. Human brain imaging suggests that the medial prefrontal cortex (mPFC) is involved in processing the emotional and motivational components of itching. In this study, we investigated the mechanisms by which glutamatergic and GABAergic neurons in mPFC differentially regulated pruritic sensation and emotion through cannabinoid type 1 receptors (CB1Rs). Chloroquinoline (CQ)-induced acute and calcipotriol (MC903)-induced chronic itch models were established. Fiberoptic calcium imaging was used to detect the activity of the two types of neurons in response to itching. The CB1R antagonist AM251 (0.5mg in 200 nL) was microinjected into the mPFC through the implanted cannula. We showed that chemogenetic activation of glutamatergic neurons and inhibition of GABAergic neurons in the mPFC reduced scratching and chronic itch-induced anxiety. GABAergic, but not glutamatergic, neurons were involved in acute itch-induced aversion. CB1Rs on glutamatergic and GABAergic neurons modulated chronic itch-induced scratching and anxiety in divergent manners. However, CB1Rs did not affect acute itch-induced scratching. CB1Rs on GABAergic, but not glutamatergic, neurons regulated acute itch-induced aversion. These results may guide the development of therapeutic strategies targeting CB1Rs to treat itch-induced sensory and emotional responses.

DOI: 10.1038/s41401-024-01426-1

Source: https://www.nature.com/articles/s41401-024-01426-1