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AMPA/海人藻酸受体阻断对大鼠伏隔核核心区和壳区多巴胺受体激动剂反应的影响。

Effects of AMPA/kainate receptor blockade on responses to dopamine receptor agonists in the core and shell of the rat nucleus accumbens.

作者信息

Choi K H, Zarandi B, Todd K G, Biondo A M, Greenshaw A J

机构信息

Department of Psychiatry, University of Alberta, Edmonton, Canada.

出版信息

Psychopharmacology (Berl). 2000 May;150(1):102-11. doi: 10.1007/s002130000391.

Abstract

The present experiments were conducted to investigate effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleprionic acid (AMPA)/kainate receptor blockade (CNQX, NBQX) on locomotor responses to D2/3 (7-OH-DPAT) and D1 [(+)-SKF 38393] dopamine receptor agonists in the nucleus accumbens (NAS) core and shell. CNQX (0.25-0.5 microgram) microinjected into the NAS core or shell did not affect baseline locomotor activity. 7-OH-DPAT (2.5-5 micrograms) decreased locomotor activity. Co-administration of CNQX (0.5 microgram) increased the effects of 7-OH-DPAT (5 micrograms) in the NAS core and shell. A similar increase was observed with NBQX (0.5 microgram) in the NAS shell. (+)-SKF 38393 (5 micrograms) into the NAS core and shell increased locomotor activity after 30 min; this effect was not altered by CNQX (0.5 microgram). As the D2/3 dopamine agonist (-)-quinpirole (2 micrograms) increased effects of (+)-SKF 38393 (5 micrograms) in NAS shell but not core, lack of site-selective effects of (+)-SKF-38393 and of 7-OH-DPAT within NAS is not attributable to drug diffusion. The previous observation that glutamate effects on locomotor activity depend on the relative involvement of D1 or D2/3 dopamine receptors in the NAS was based on the dopamine-depletion model. The present results demonstrate differential interactions of AMPA receptor blockade with dopamine agonists in "dopamine-intact" animals.

摘要

进行本实验以研究α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)/海人藻酸受体阻断剂(CNQX、NBQX)对伏隔核(NAS)核心区和壳区中D2/3(7-羟基-DPAT)和D1[(+)-SKF 38393]多巴胺受体激动剂引起的运动反应的影响。向NAS核心区或壳区微量注射CNQX(0.25 - 0.5微克)不影响基础运动活性。7-羟基-DPAT(2.5 - 5微克)降低运动活性。联合给予CNQX(0.5微克)增强了7-羟基-DPAT(5微克)在NAS核心区和壳区的作用。在NAS壳区,NBQX(0.5微克)也观察到类似的增强作用。向NAS核心区和壳区注射(+)-SKF 38393(5微克)30分钟后增加运动活性;这种作用不受CNQX(0.5微克)影响。由于D2/3多巴胺激动剂(-)-喹吡罗(2微克)增强了(+)-SKF 38393(5微克)在NAS壳区而非核心区的作用,(+)-SKF-38393和7-羟基-DPAT在NAS内缺乏位点选择性作用并非归因于药物扩散。先前关于谷氨酸对运动活性的影响取决于NAS中D1或D2/3多巴胺受体相对参与情况的观察是基于多巴胺耗竭模型。本研究结果表明在“多巴胺完整”动物中,AMPA受体阻断剂与多巴胺激动剂存在不同的相互作用。

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