Westerink B H, Santiago M, De Vries J B
Department of Medicinal Chemistry, University of Groningen, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1992 Dec;346(6):637-43. doi: 10.1007/BF00168736.
In the present study we have administered prototypical drugs of 5 different receptors (D-2, GABA-A, GABA-B, NMDA, kainate) to the substantia nigra by infusion via a microdialysis probe, whereas the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were recorded both in the substantia nigra and (by a second microdialysis probe) in the ipsilateral striatum. Infusion of the specific D-2 receptor agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin ((--)-N0437) into the nigra induced a decrease in the release of dopamine in the nigra (after 1 mumol/l) as well as in the ipsilateral striatum (after 10 mumol/l). During these infusions extracellular DOPAC decreased in the nigra and increased in the striatum. Infusion of the D-2 specific receptor antagonist (--)-sulpiride into the nigra induced an increase in the release of dopamine in the nigra (after 1 mumol/l) as well as in the ipsilateral striatum (10 mumol/l). During these infusions a slight increase of extracellular DOPAC was noticed in the nigra. Infusion of the GABA-A receptor antagonist bicuculline into the nigra (50 mumol/l) induced an increase in the release of dopamine and DOPAC both in the nigra and ipsilateral striatum. Infusion of the GABA-B receptor agonist d,I-baclofen into the nigra (10 mumol/l) induced a decrease of in the release of dopamine in the nigra as well as in the ipsilateral striatum, whereas extracellular DOPAC decreased in the nigra and increased in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
在本研究中,我们通过微透析探针向黑质注入了5种不同受体(D-2、GABA-A、GABA-B、NMDA、海人藻酸)的原型药物,同时在黑质以及(通过第二个微透析探针)同侧纹状体中记录多巴胺和3,4-二羟基苯乙酸(DOPAC)的释放情况。向黑质注入特异性D-2受体激动剂2-(N-丙基-N-2-噻吩基乙氨基)-5-羟基四氢萘((-)-N0437),在黑质中(1 μmol/L后)以及同侧纹状体中(10 μmol/L后)可诱导多巴胺释放减少。在这些注入过程中,黑质细胞外DOPAC减少,而纹状体中增加。向黑质注入D-2特异性受体拮抗剂(-)-舒必利,在黑质中(1 μmol/L后)以及同侧纹状体中(10 μmol/L)可诱导多巴胺释放增加。在这些注入过程中,黑质细胞外DOPAC略有增加。向黑质注入GABA-A受体拮抗剂荷包牡丹碱(50 μmol/L),可诱导黑质和同侧纹状体中多巴胺和DOPAC释放增加。向黑质注入GABA-B受体激动剂d,l-巴氯芬(10 μmol/L),可诱导黑质以及同侧纹状体中多巴胺释放减少,而黑质细胞外DOPAC减少,纹状体中增加。(摘要截选至250字)