Ossowska K, Konieczny J, Wardas J, Gołembiowska K, Wolfarth S, Pilc A
Department of Neuro-Psychopharmacology, Institute of Pharmacology, kraksów, Poland.
Amino Acids. 2002;23(1-3):193-8. doi: 10.1007/s00726-001-0128-0.
The primary cause of Parkinson's disease is a loss of dopamine in the corpus striatum. It has been postulated that this effect leads to disinhibition of the striopallidal pathway and secondarily, to a functional shift towards glutamatergic stimulation. The aim of the present study was to find out whether inhibition of glutamatergic transmission at a level of metabotropic glutamate receptors (mGluRs) in the striatum may alleviate parkinsonian-like symptoms in rats. The non-competitive antagonist of receptor subtype 5 (mGluR5), MPEP (1.0-10 mg/kg ip), or the agonist of group II mGluRs, LY354,740 (5-10 mg/kg ip), reduced haloperidol-induced muscle rigidity and catalepsy. Intrastriatal injections of the mGluR1 antagonist, (RS) AIDA (7.5-15 microg/0.5 microl), but not of the agonist of group II mGluRs, 2R,4R-APDC (7.5-15 microg/0.5 microl), inhibited the muscle rigidity induced by haloperidol. In order to search for an influence of mGluRs on the striopallidal pathway, the effect of MPEP or of the agonist of group II mGluRs, DCG-IV, on the proenkephalin (PENK) mRNA expression in the dorso-lateral striatum was examined by an in situ hybridization. Repeated MPEP (6 x 10 mg/kg ip) administration did not influence PENK expression in naïve rats, but diminished that increased by haloperidol. In contrast, repeated DCG-IV (3 x 1 nmol/4 microl icv) injections enhanced both the control and the haloperidol-increased levels of PENK expression. The obtained results suggest that blockade of group I mGluRs, or stimulation of group II mGluRs may be important to ameliorate parkinsonian symptoms. Striatal mGluRs may contribute to at least some of these effects.
帕金森病的主要病因是纹状体中多巴胺的缺失。据推测，这种效应会导致纹状体苍白球通路的去抑制，进而导致功能向谷氨酸能刺激转变。本研究的目的是探究在纹状体代谢型谷氨酸受体（mGluRs）水平抑制谷氨酸能传递是否可减轻大鼠的帕金森样症状。受体亚型5（mGluR5）的非竞争性拮抗剂MPEP（1.0 - 10 mg/kg，腹腔注射）或II组mGluRs的激动剂LY354,740（5 - 10 mg/kg，腹腔注射）可减轻氟哌啶醇诱导的肌肉强直和僵住症。纹状体内注射mGluR1拮抗剂（RS）AIDA（7.5 - 15 μg/0.5 μl）可抑制氟哌啶醇诱导的肌肉强直，但II组mGluRs的激动剂2R,4R - APDC（7.5 - 15 μg/0.5 μl）则无此作用。为了探究mGluRs对纹状体苍白球通路的影响，通过原位杂交检测了MPEP或II组mGluRs的激动剂DCG - IV对背外侧纹状体中前脑啡肽（PENK）mRNA表达的影响。重复给予MPEP（6×10 mg/kg，腹腔注射）对未处理大鼠的PENK表达无影响，但可降低氟哌啶醇诱导增加的PENK表达。相反，重复注射DCG - IV（3×1 nmol/4 μl，脑室内注射）可增强PENK表达的基础水平以及氟哌啶醇诱导增加的水平。所得结果表明，阻断I组mGluRs或刺激II组mGluRs可能对改善帕金森症状很重要。纹状体mGluRs可能至少在部分这些效应中起作用。
