Zhao ZhengLin, Kim Sang Chan, Zhao RongJie, Wu YiYan, Zhang Jie, Liu HongFeng, Kim Young Woo, Zhu XiaoDong, Gu ChangHong, Lee Chul Won, Lee Bong Hyo, Jang Eun Young, Ko Hae Li, Yang Chae Ha
Department of Pharmacology, Mudanjiang Medical University, Mudanjiang 157011, China.
College of Oriental Medicine, Daegu Haany University, Daegu 706-060, South Korea.
Neurosci Lett. 2015 Jun 15;597:143-8. doi: 10.1016/j.neulet.2015.04.045. Epub 2015 Apr 30.
This study investigated the involvement of the mesolimbic dopamine (DA) system in the anxiolytic effects of acupuncture during ethanol withdrawal (EW). Rats were intraperitoneally treated with 3g/kg/day of ethanol for 28 days and experienced 3 days of withdrawal. During EW, the rats were bilaterally treated with acupuncture at acupoints HT7 (Shenmen) or PC6 (Neiguan) or at a non-acupoint (tail) once daily for 1min over 3 days. High-performance liquid chromatographic (HPLC) analysis showed that EW significantly decreased both DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens shell (NaccSh); however, these processes were inhibited by acupuncture at HT7 but not at PC6. Real-time polymerase chain reaction and western blot assays also revealed that acupuncture at HT7 prevented the EW-induced reductions in tyrosine hydroxylase mRNA expression in the ventral tegmental area (VTA) and tyrosine hydroxylase protein expression in the NaccSh. A prior intra-NaccSh infusion of a cocktail of the selective DA1 receptor antagonist SCH23390 and the selective DA2 receptor antagonist eticlopride blocked the anxiolytic effect of acupuncture at HT7 in elevated plus maze tests. In addition, acupuncture at HT7 suppressed EW-induced increased BDNF levels in the VTA. These findings suggest that acupuncture at HT7 improves the VTA-Nacc DAergic function via inhibition of BDNF expression in the VTA, thereby exerting anxiolytic effects during EW.
本研究调查了中脑边缘多巴胺（DA）系统在乙醇戒断（EW）期间针刺抗焦虑作用中的参与情况。大鼠腹腔注射3g/kg/天的乙醇，持续28天，然后经历3天的戒断期。在EW期间，大鼠每天双侧针刺穴位HT7（神门）或PC6（内关）或非穴位（尾巴）1分钟，持续3天。高效液相色谱（HPLC）分析表明，EW显著降低了伏隔核壳（NaccSh）中的DA和3,4-二羟基苯乙酸（DOPAC）水平；然而，HT7针刺可抑制这些过程，而PC6针刺则不能。实时聚合酶链反应和蛋白质印迹分析还显示，HT7针刺可防止EW诱导的腹侧被盖区（VTA）酪氨酸羟化酶mRNA表达降低以及NaccSh中酪氨酸羟化酶蛋白表达降低。在高架十字迷宫试验中，预先向NaccSh内注射选择性DA1受体拮抗剂SCH23390和选择性DA2受体拮抗剂依替必利的混合物可阻断HT7针刺的抗焦虑作用。此外，HT7针刺可抑制EW诱导的VTA中脑源性神经营养因子（BDNF）水平升高。这些发现表明，HT7针刺通过抑制VTA中BDNF的表达来改善VTA-Nacc多巴胺能功能，从而在EW期间发挥抗焦虑作用。
