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大鼠前扣带皮层多巴胺D1受体参与痛相关情绪调节的行为-电生理学观察

杜相欣¹, 张利娜¹, 张雨彤¹, 郝娜¹, 郭霞¹, 赵欣¹, 王志华², 张宇^1,*

¹山西医科大学细胞生理学教育部重点实验室，生理学系，太原 030001；²山西医科大学病理教研室，太原 030001

摘要

本研究旨在探索前扣带皮层(anterior cingulate cortex, ACC)的多巴胺D1受体参与痛情绪反应的调节作用。第一天大鼠适应环境并记录检测指标的基础值；第二天预先在ACC给予多巴胺D1受体拮抗剂SCH-23390或激动剂SKF-38393，然后大鼠左后足底注射完全弗氏佐剂(complete Freund’s adjuvant, CFA, 0.08 mL)，与特定环境匹配后建立条件位置逃避(conditioned place avoidance, CPA)反应；第三天同步观察大鼠在痛环境中的CPA反应与ACC脑区神经元的放电频率，随后进行旷场行为、机械痛行为和热缩足反射潜伏期(paw withdrawal latency, PWL)测试；在另外一组实验中，给予大鼠足底注射生理盐水(NS)，ACC脑区预先给予多巴胺D1受体拮抗剂或激动剂，并进行上述同样的实验观察。结果显示：(1) 相比于对照组，足底注射CFA的大鼠PWL与机械痛阈值明显降低(P < 0.05)；(2) 注射CFA组的大鼠在“痛环境”和旷场中心的停留时间明显缩短(P < 0.05)；(3) 预先在ACC注射拮抗剂SCH-23390 (10 μg)可缓解CFA所致的焦虑样负性情绪反应(P < 0.05)，并反转CFA诱发ACC脑区神经元放电频率增加(P < 0.05)；(4) 预先在ACC注射激动剂SKF-38393 (10 μg)可以引起足底注射NS大鼠产生类似CPA样的行为反应，且ACC脑区神经元放电频率增加(P < 0.05)；(5)免疫荧光双标结果显示，多巴胺D1受体与NMDA受体共表达于同一神经元上。以上结果提示，抑制ACC脑区的多巴胺D1受体可以缓解持续性痛诱发的负性情绪反应。  

关键词： 多巴胺D1受体; 前扣带皮层; 完全弗氏佐剂; 痛相关情绪; 多通道电生理学

Behavioral-electrophysiological observation of the involvement of dopamine D1 receptor of the rat anterior cingulate cortex in the regulation of pain-related emotion 

DU Xiang-Xin¹, ZHANG Li-Na¹, ZHANG Yu-Tong¹, HAO Na¹, GUO Xia¹, ZHAO Xin¹, WANG Zhi-Hua², ZHANG Yu^1,*

¹Department of Physiology, Key Laboratory of Cell Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China；²Department of Pathology, Shanxi Medical University, Taiyuan 030001, China

Abstract

The present study was aimed to explore the involvement of dopamine D1 receptor of the anterior cingulate cortex (ACC) in the regulation of chronic inflammatory pain-related emotion. On the first day, the rats were acclimated to the environment and the baseline indices were measured. On the second day, the rats were administered with the dopamine D1 receptor antagonist SCH-23390 or agonist SKF38393 in the ACC, and then they were subcutaneously injected with complete Freund’s adjuvant (CFA, 0.08 mL) in the left hind paw to establish conditioned place avoidance (CPA) response after pairing with specific environment. On the third day, the CPA response and the firing frequency of ACC neurons were observed synchronously, and the open-field behavior, mechanical pain behavior and paw withdrawal latency (PWL) tests were also observed subsequently. In other experiments, rats were given subcutaneous injection of normal saline (NS) on the left hind paw after SCH-23390 or SKF-38393 was administered in the ACC, and then the same observations were performed. The results showed that: (1) Compared with the control group, the PWL and mechanical pain thresholds of rats injected with CFA on the left hind paw were significantly decreased (P < 0.05); (2) The residence time of rats injected with CFA in the “pain environment” and open field center was significantly shortened (P < 0.05); (3) Pre-injection of antagonist SCH-23390 in ACC (10 μg) alleviated the anxiety-like negative behavior response induced by CFA (P < 0.05) and reversed CFA-induced increases of discharge frequency of ACC neurons (P < 0.05); (4) Pre-injection of agonist SKF-38393 in the ACC (10 μg) induced CPA-like behavioral response in rats injected with NS in the left hind paw, and increased the firing frequency of ACC neurons (P < 0.05); (5) Immunofluorescence detection showed that dopamine D1 receptor and NMDA receptor were co-expressed in the same neuron. These results suggest that inhibition of dopamine D1 receptor in ACC can alleviate the negative emotional response induced by persistent pain.  

Key words: dopamine D1 receptor; anterior cingulate cortex; complete Freund’s adjuvant; pain-related emotions; multi-channel electrophysiology

收稿日期：　　录用日期：

通讯作者：张宇　　E-mail: zhyucnm@163.com

DOI: 10.13294/j.aps.2022.0026

引用本文：

杜相欣, 张利娜, 张雨彤, 郝娜, 郭霞, 赵欣, 王志华, 张宇. 大鼠前扣带皮层多巴胺D1受体参与痛相关情绪调节的行为-电生理学观察[J]. 生理学报 2022; 74 (2): 155-164.

DU Xiang-Xin, ZHANG Li-Na, ZHANG Yu-Tong, HAO Na, GUO Xia, ZHAO Xin, WANG Zhi-Hua. Behavioral-electrophysiological observation of the involvement of dopamine D1 receptor of the rat anterior cingulate cortex in the regulation of pain-related emotion . Acta Physiol Sin 2022; 74 (2): 155-164 (in Chinese with English abstract).