左旋千金藤啶碱D_1激动-D_2 阻滞作用引起伏核双相放电活动的电生理研究(英文)  

Electrophysiological study on biphasic firing activity elicited by D_1 agonistic-D_2 antagonistic action of (-)-stepholidine in nucleus accumbens

作　　者：朱子涛[1] 傅雨[1] 胡国渊 金国章 

机构地区：[1]中国科学院上海药物研究所神经药理研究室,上海200031

出　　处：《生理学报》2000年第2期123-130,共8页Acta Physiologica Sinica

基　　金：SupportedbytheNationalNaturalScienceFoundationofChina(No39670829)

摘　　要：为确定左旋千金藤啶碱 (SPD)对中脑边缘DA神经系统的作用特性 ,本研究采用细胞外记录的电生理学方法 ,观察微电泳和尾静脉给药对 6 OHDA损毁及未损毁大鼠的伏核 (NAc)单位放电的影响。结果显示 :SPD累积给药 ( 0 0 2～ 2mg/kg,iv)可诱发NAc神经元双相放电特征 ,即小剂量抑制、大剂量兴奋。预先给予D2 受体拮抗剂spiperone ,SPD则仅产生兴奋效应 ,并被D1拮抗剂SCH 2 3390所翻转或阻断 ,提示SPD对NAc神经元放电有D1激动特性。另一方面 ,大剂量SPD完全翻转D2 激动剂LY 1715 5 5和D1/D2 混合型激动剂阿朴吗啡对NAc神经元的抑制作用 ,表明SPD还具有D2 受体的阻滞特性。与静脉给药不同 ,NAc内微电泳SPD ( 30mmol/L ,2 0～ 80nA)很难诱发该神经核的兴奋或抑制性放电 ,而微电泳D1激动剂SKF 38393能产生明显的放电抑制效应。然而 ,在 6 OHDA损毁大鼠 ,微电泳SPD可使绝大多数NAc神经元 ( 91% )放电抑制 ,并为D1阻滞剂SCH 2 3390所完全拮抗 ,而不受D2 阻滞剂spiperone的影响。以上结果表明 ,SPD对NAc神经元活动具有‘D2 阻滞 D1激动’的双重药理作用特性 ,后者与SPD作用于mPFC的D1受体有密切关系 。Our previous work has demonstrated that ( ) stepholidine (SPD) has dual action, ie D 1 agonistic D 2 antagonistic action on DA receptors in the nigra striatal dopamine (DA) system. The present study attempted to ascertain its dual action on the mesolimbic DA system. The firing activities of the nucleus accumbens (NAc) neurons were extracellularly recorded with intravenous and iontophoretic administration of the drug in 6 hydroxydopamine (6 OHDA) lesioned and intact rats. The results showed that SPD produced a consistently biphasic firing of NAc neurons during the cumulative doses of 0 02～2 mg/kg, iv. When the rats were pretreated with D 2 antagonist spiperone, SPD only exerted an increasing effect, which was subsequently reversed by the D 1 antagonist SCH 23390 Moreover, SCH 23390 could prevent the rate of increase elicited by SPD at high doses, presumably due to the D 1 agonistic action of SPD on the activity of NAc neuron. On the other hand, the inhibition of NAc firing elicited by either D 2 agonist LY171555 or D 1/D 2 agonists apomorphine was completely reversed by SPD, suggesting an antagonistic action of SPD to D 2 receptors. In 6 OHDA lesioned rats, iontophoresis of SPD also had an inhibitory effect in the majority of NAc neurons (91%) as SKF 38393 did. This inhibition could be completely blocked by the ejection of SCH 23390, but not by spiperone. These results indicate that SPD also has a D 1 agonistic D 2 antagonistic dual action on NAc neuron activity, which may be beneficial to the treatment of schizophrenia.

关 键 词：左旋千金藤啶碱 多巴胺受体 伏核 电生理 

分 类 号：Q424[生物学—神经生物学] R338[生物学—生理学]