De Boer P, Enrico P, Wright J, Wise L D, Timmerman W, Moor E, Dijkstra D, Wikström H V, Westerink B H
University Center for Pharmacy, Department of Medicinal Chemistry, University of Groningen, The Netherlands.
Brain Res. 1997 May 30;758(1-2):83-91. doi: 10.1016/s0006-8993(96)01438-2.
By examining the effect of dopamine (DA) D3 receptor stimulation on locomotor activity and extracellular levels of DA in striatum we show that inhibition of locomotor activity induced by DA D3 receptor-selective agonists is mediated by two interacting mechanisms: (1) directly via the stimulation of DA D3 receptors that inhibit locomotor activity, and (2) indirectly via a decrease in extracellular levels of DA. Thus, the moderately DA D3 receptor-selective agonist R-(+)-7-OH- DPAT (R-(+)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin) decreased locomotor activity after administration of 10 nmol/kg and extracellular DA levels in accumbens and striatum after administration of 30 nmol/kg. A decrease in locomotor activity that coincided with a decrease in extracellular DA levels in striatum was observed after administration of 100 nmol/kg of the DA D3 receptor-selective agonist PD128907 ((+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3 b]-1,4-oxasin-9-ol. In combination with the partial, DA D3 receptor-selective agonist PD151328 (2-[4[3-(4-phenyl)-1- piperazinyl)propoxy]phenyl]-benzamidazole), a reversal of the attenuating effect of PD128907 on locomotor activity was observed, without an effect on extracellular levels of DA. In combination with a low--10 nmol/kg--dose of haloperidol, a reversal of the inhibitory effect of PD128907 on locomotor activity was observed that coincided with an increase in extracellular levels of DA. In the presence of 0.5 mg/kg amphetamine, PD128907 decreased amphetamine-induced locomotor activity. This effect could be reversed by PD151328.
通过研究多巴胺（DA）D3受体刺激对运动活性及纹状体中DA细胞外水平的影响，我们发现DA D3受体选择性激动剂诱导的运动活性抑制由两种相互作用的机制介导：（1）直接通过刺激抑制运动活性的DA D3受体，以及（2）间接通过降低DA的细胞外水平。因此，中等DA D3受体选择性激动剂R-(+)-7-OH-DPAT（R-(+)-7-羟基-2-(N,N-二正丙基氨基)四氢萘）在给予10 nmol/kg后降低了运动活性，在给予30 nmol/kg后降低了伏隔核和纹状体中的细胞外DA水平。在给予100 nmol/kg的DA D3受体选择性激动剂PD128907（(+)-反式-3,4,4a,10b-四氢-4-丙基-2H,5H-[1]苯并吡喃并[4,3-b]-1,4-恶嗪-9-醇）后，观察到运动活性降低，同时纹状体中细胞外DA水平也降低。与部分DA D3受体选择性激动剂PD151328（2-[4-[3-(4-苯基)-1-哌嗪基]丙氧基]苯基]-苯甲酰胺）联合使用时，观察到PD128907对运动活性的减弱作用出现逆转，而对细胞外DA水平无影响。与低剂量——10 nmol/kg——的氟哌啶醇联合使用时，观察到PD128907对运动活性的抑制作用出现逆转，同时细胞外DA水平升高。在存在0.5 mg/kg苯丙胺的情况下，PD128907降低了苯丙胺诱导的运动活性。这种作用可被PD151328逆转。
