Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its correlation with DA receptor subtypes

作     者：Yu FU2,3,4, Zi-tao ZHU2,5, Xing-zu ZHU2, Guo-zhang JIN2,6 2State KeyLaboratory of Drug Research,Shanghai Institute ofMateria Medica, Shanghai Institutes for BiologicalSciences, ChineseAcademy of Sciences, Graduate Schoolof the Chinese Academy of Sciences, Shanghai 201203, ChinaNow in Department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA, 

作者机构：中科院上海生命科学院 State Key Laboratory of Drug ResearchChinese Academy of Sciences 

出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))

年 卷 期：2004年第25卷第12期

页      面：31-39页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：Project supported by the National Natural Science Foundation of China (No 30271495 39870898) 

主　　题：berberine dopamine D1 receptors dopamine D2 receptors nucleus accumbens 

摘      要：AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antago- nist action on meso-accumbens-mPFC DA system. METHODS: Single unit spontaneous firing activity was re- corded in the nucleus accumbens (NAc) neurons of na?ve and unilateral-6-hydroxydopamine (6-OHDA)-lesioned Sprague-Dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by the change of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced a decrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB-18 was capable of reversing the inhibition induced by both D2 agonist LY171555 and D1/D2 agonist APO on NAc firing activity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which was reversed by the D1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited by iontophoretically applied THPB-18 in 90 % of 6-OHDA-lesioned rats, while THPB-18 caused variable effects on the firing of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked by iontophoretic application of SCH23390, but not D2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine, THPB-18 also possesses the “D1 agonistic-D2 antagonistic dual action on the VTA-NAc DA system.4Now in Department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,4Now in Department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,