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左旋千金藤立定增强mPFC DA受体对皮层下NAc DA释放的抑制作用(英文)

l-Stepholidine facilitates inhibition of mPFC DA receptors on subcortical NAc DA release

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【作者】 朱子涛吴蔚然傅雨金国章

【Author】 ZHU Zi-Tao, WU Wei-Ran, FU Yu, JIN Guo-Zhang(Department of Pharmacology, Shanghai Institute of Materia Medica , Shanghai 200031, China)Now in Dept of Physiology & Pharmacology,Oregon Health Sciences University,Portland,OR 97201-3098,USA

【机构】 中国科学院上海药物研究所中国科学院上海药物研究所 上海中国 200031上海中国 200031

【摘要】 目的:研究左旋千金藤立定(SPD)激动内侧前额皮层(mPFC)D1受体对皮层下伏隔核DA诱发释放的影响。方法:6-羟基多巴胺损伤大鼠mPFC两周后,同侧皮层内微量注射SPD,微透析检测电刺激中脑腹侧被盖区(VTA)或苯丙胺(AMP)诱导的NAc DA释放。结果:mPFC DA耗竭未改变NAc DA的基础水平和电刺激VTA诱发的DA释放,却明显易化AMP灌流诱发的NAc DA释放,表明mPFC DA系统参与调节NAc DA的诱发释放。mPFC内微量注射SPD未能改变电刺激VTA诱发的DA释放,但显著减弱AMP对NAc DA的诱发释放;该作用可被D1拮抗剂Sch-23390部分翻转,而D2拮抗剂spiperone无作用。结论:SPD强化mPFC D1受体对皮层下伏隔核DA释放的抑制性调节作用。

【Abstract】 tion of DA release in the NAc.To determine whether the D1 agonistic action of (-)-stepholidine (SPD) on the medial prefrontal cortex (mPFC) neuron is involved in the modulation of evoked subcortical dopamine (DA) release from nucleus accum-bens (NAc) of rats. METHODS: With the microinjec-tion of SPD into the mPFC, the ventral tegmental area (VTA)-stimulated or amphetamine (AMP)-evoked DA efflux in the NAc was detected by microdialysis + HPLC-ECD in the 6-hydroxydopamine (6-OHDA)-lesioned and intact rats. RESULTS: The depletion of DA in the mPFC did not modify both the basal level and the VTA-stimulated DA efflux in the NAc, but significantly facilitated the AMP (20μmol·L-1)-evoked DA efflux within the NAc. It indicates that the mPFC DA system is involved in the regulation of evoked DA release in the NAc. Besides, the AMP-evoked increase of the extracellular DA release in the NAc was significantly attenuated by SPD (10, 30 mmol·L-1) microinjection into the mPFC, though this injection of SPD could not alter the response of DA release by the stimulation of the VTA. Furthermore, the inhibitory effect of SPD on the AMP-evoked DA efflux could be partially reversed by intravenous administration of D1 antagonist Sch-23390 (1 mg·kg-1), but not by D2 antagonist spiperone. CONCLUSION: SPD is capable of enhancing the function of D1 receptors in the mPFC, by which it facilitates the inhibi-

【基金】 Project supported by the National Natural Science Foundation of China, № 39670829, 39770853.
  • 【文献出处】 Acta Pharmacologica Sinica ,中国药理学报(英文版) , 编辑部邮箱 ,2000年07期
  • 【分类号】R96
  • 【被引频次】6
  • 【下载频次】49
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