Konieczny J, Wardas J, Kuter K, Pilc A, Ossowska K
Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343, Kraków, Poland.
Neuroscience. 2007 Mar 16;145(2):611-20. doi: 10.1016/j.neuroscience.2006.12.006. Epub 2007 Jan 16.
Group III metabotropic glutamate receptors (mGluRs) are widely distributed in the basal ganglia, especially on the terminals of pathways which seem to be overactive in Parkinson's disease. The aim of the present study was to determine whether (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-1), an agonist of group III mGluRs, injected bilaterally into the globus pallidus (GP), striatum or substantia nigra pars reticulata (SNr), can attenuate the haloperidol-induced catalepsy in rats, and whether that effect was related to modulation of proenkephalin (PENK) or prodynorphin (PDYN) mRNA expression in the striatum. Administration of ACPT-1 (0.05-1.6 microg/0.5 microl/side) caused a dose-and-structure-dependent decrease in the haloperidol (0.5 mg/kg i.p. or 1.5 mg/kg s.c.)-induced catalepsy whose order was as follows: GP>striatum>SNr. ACPT-1, given alone to any of those structures, induced no catalepsy in rats. Haloperidol (3 x 1.5 mg/kg s.c.) significantly increased PENK mRNA expression in the striatum, while PDYN mRNA levels were not affected by that treatment. ACPT-1 (3 x 1.6 microg/0.5 microl/side) injected into the striatum significantly attenuated the haloperidol-increased PENK mRNA expression, whereas administration of that compound into the GP or SNr did not influence the haloperidol-increased striatal PENK mRNA levels. Our results demonstrate that stimulation of group III mGluRs in the striatum, GP or SNr exerts antiparkinsonian-like effects in rats. The anticataleptic effect of intrastriatally injected ACPT-1 seems to correlate with diminished striatal PENK mRNA expression. However, since the anticataleptic effect produced by intrapallidal and intranigral injection of ACPT-1 is not related to a simultaneous decrease in striatal PENK mRNA levels, it is likely that a decrease in enkephalin biosynthesis is not a necessary condition to obtain an antiparkinsonian effect.
III 组代谢型谷氨酸受体（mGluRs）广泛分布于基底神经节，尤其是在帕金森病中似乎过度活跃的通路的终末。本研究的目的是确定双侧注射到苍白球（GP）、纹状体或黑质网状部（SNr）的 III 组 mGluRs 激动剂（1S,3R,4S）-1-氨基环戊烷-1,3,4-三羧酸（ACPT-1）是否能减轻氟哌啶醇诱导的大鼠僵住症，以及该效应是否与纹状体中前脑啡肽（PENK）或前强啡肽（PDYN）mRNA 表达的调节有关。给予 ACPT-1（0.05 - 1.6 μg/0.5 μl/侧）导致氟哌啶醇（0.5 mg/kg 腹腔注射或 1.5 mg/kg 皮下注射）诱导的僵住症呈剂量和结构依赖性降低，其顺序如下：GP＞纹状体＞SNr。单独给予 ACPT-1 到这些结构中的任何一个，均未在大鼠中诱导出僵住症。氟哌啶醇（3×1.5 mg/kg 皮下注射）显著增加纹状体中 PENK mRNA 的表达，而 PDYN mRNA 水平不受该处理的影响。注射到纹状体中的 ACPT-1（3×1.6 μg/0.5 μl/侧）显著减弱氟哌啶醇增加的 PENK mRNA 表达，而将该化合物注射到 GP 或 SNr 中并不影响氟哌啶醇增加的纹状体 PENK mRNA 水平。我们的结果表明，刺激纹状体、GP 或 SNr 中的 III 组 mGluRs 在大鼠中发挥抗帕金森样作用。纹状体内注射 ACPT-1 的抗僵住症作用似乎与纹状体 PENK mRNA 表达减少相关。然而，由于苍白球内和黑质内注射 ACPT-1 产生的抗僵住症作用与纹状体 PENK mRNA 水平的同时降低无关，因此脑啡肽生物合成的减少可能不是获得抗帕金森病效应的必要条件。
