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In the present study, the possible changes in the expression of metabotropic glutamate receptors (mGluRs) were examined in the basal ganglia of a primate model for Parkinson's disease. When the patterns of immunohistochemical localization of mGluRs in monkeys administered systemically with 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) were analysed in comparison with normal controls, we found that expression of mGluR1\u03b1, but not of other subtypes, was significantly reduced in the internal and external segments of the globus pallidus and the substantia nigra pars reticulata. To elucidate the functional role of mGluR1 in the control of pallidal neuron activity, extracellular unit recordings combined with intrapallidal microinjections of mGluR1\u2010related agents were then performed in normal and parkinsonian monkeys. In normal awake conditions, the spontaneous firing rates of neurons in the pallidal complex were increased by DHPG, a selective agonist of group I mGluRs, whereas they were decreased by AIDA, a selective antagonist of group I mGluRs, or LY367385, a selective antagonist of mGluR1. These electrophysiological data strongly indicate that the excitatory mechanism of pallidal neurons by glutamate is mediated at least partly through mGluR1. The effects of the mGluR1\u2010related agents on neuronal firing in the internal pallidal segment became rather obscure after MPTP treatment. Our results suggest that the specific down\u2010regulation of pallidal and nigral mGluR1\u03b1 in the parkinsonian state may exert a compensatory action to reverse the overactivity of the subthalamic nucleus\u2010derived glutamatergic input that is generated in the disease.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2005.04488.x","type":"journal-article","created":{"date-parts":[[2005,12,5]],"date-time":"2005-12-05T15:32:24Z","timestamp":1133796744000},"page":"3241-3254","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Down\u2010regulation of metabotropic glutamate receptor 1\u03b1 in globus pallidus and substantia nigra of parkinsonian monkeys"],"prefix":"10.1111","volume":"22","author":[{"given":"K.","family":"Kaneda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Tachibana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Imanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Shigemoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Nambu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(89)90074-X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(98)00050-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-21-07871.2000"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870060404"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-02-00592.2002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2003.11.001"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1993.tb00505.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.060061"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2402638"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.72.2.507"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960513)368:4<553::AID-CNE7>3.0.CO;2-3"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00670-2"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.741166.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-17-06853.2001"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(99)00067-2"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01563-1"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990428)407:1<33::AID-CNE3>3.0.CO;2-G"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00377-4"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870060208"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.37.1.205"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00371.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(90)90110-V"},{"key":"e_1_2_7_24_1","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/S0026-895X(24)23206-5","article-title":"Alterations in subunit expression, composition, and phosphorylation of striatal N\u2010methyl\u2010d\u2010aspartate glutamate receptors in a rat 6\u2010hydroxydopamine model of Parkinson's disease","volume":"57","author":"Dunah A.W.","year":"2000","journal-title":"Mol. 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