Fu Yu, Zhu Zi-tao, Zhu Xin-zu, Jin Guo-zhang
State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Acta Pharmacol Sin. 2004 Dec;25(12):1597-605.
To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antagonist action on meso-accumbens-mPFC DA system.
Single unit spontaneous firing activity was recorded in the nucleus accumbens (NAc) neurons of naive 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.
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.
Similar to L-stepholidine, THPB-18 also possesses the D1 agonistic-D2 antagonistic dual action on the VTA-NAc DA system.
研究THPB-18（l-12-氯非洲防己碱）对中脑-伏隔核-内侧前额叶皮质多巴胺（DA）系统是否具有D1激动剂-D2拮抗剂作用。
记录未处理及单侧6-羟基多巴胺（6-OHDA）损伤的Sprague-Dawley大鼠伏隔核（NAc）神经元的单单位自发放电活动。通过放电频率的变化确定静脉注射或离子导入药物的作用。
正常情况下，累积给药时静脉注射THPB-18可使NAc神经元放电模式呈先降低后升高的双相变化。高剂量THPB-18能够逆转D2激动剂LY171555和D1/D2激动剂阿扑吗啡（APO）对NAc放电活动的抑制作用。氟哌啶醇预处理不能阻断高剂量THPB-18引起的放电频率增加，而D1选择性拮抗剂SCH23390可使其逆转。在90%的6-OHDA损伤大鼠中，离子导入THPB-18可有效抑制受试的NAc神经元，而THPB-18对未损伤大鼠神经元的NAc放电产生不同影响。离子导入SCH23390可阻断THPB-18的抑制作用，但D2拮抗剂氟哌啶醇则不能。
与左旋千金藤啶碱相似，THPB-18对腹侧被盖区-伏隔核DA系统也具有D1激动-D2拮抗的双重作用。
