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There is evidence that when given systemically, 2\u2010methyl\u20106\u2010(phenylethynyl)\u2010pyridine (MPEP), a metabotropic glutamate receptor type 5 (mGluR<jats:sub>5<\/jats:sub>) antagonist, produces anti\u2010parkinsonian effects in animal models, but the site of action has not been directly established. In the present study, we examined whether the subthalamic nucleus (STN) and its output structures may mediate such an effect using a unilateral rat model of Parkinson's disease. A battery of simple behavioral tests, reliably sensitive to dopamine depletion, was applied consecutively: (i) prior to surgery; (ii) 3\u2003weeks following a unilateral 6\u2010hydroxydopamine lesion of the substantia nigra pars compacta; (iii) at 1\u2003h, 24\u2003h and 4\u2003days following a microinjection of MPEP, via an indwelling cannula, into the STN, entopeduncular nucleus (EP) or substantia nigra zona reticulata. Unilaterally dopamine\u2010depleted animals typically had severe motor and sensorimotor asymmetries 3\u2003weeks following surgery. Microinjection of 25\u2003nmol MPEP into the STN of these animals significantly attenuated these asymmetries relative to vehicle. Further microinjections of lower doses (5 and 10\u2003nmol) revealed a dose\u2013response effect. Microinjection of MPEP into either the EP or substantia nigra zona reticulata was without effect. These data suggest that MPEP may act at the level of the STN to reduce glutamatergic overactivity and thereby induce anti\u2010parkinsonian effects.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2005.04550.x","type":"journal-article","created":{"date-parts":[[2006,1,18]],"date-time":"2006-01-18T23:36:05Z","timestamp":1137627365000},"page":"151-160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Blockade of mGluR<sub>5<\/sub> glutamate receptors in the subthalamic nucleus ameliorates motor asymmetry in an animal model of Parkinson's disease"],"prefix":"10.1111","volume":"23","author":[{"given":"Janice M.","family":"Phillips","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoa A.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry C.","family":"Ackerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel T.","family":"Maidment","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00550-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008877-199508000-00011"},{"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":"10.1111\/j.1460-9568.1993.tb00505.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.72.2.507"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-02-00599.1999"},{"key":"e_1_2_7_8_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_9_1","doi-asserted-by":"crossref","first-page":"8302","DOI":"10.1523\/JNEUROSCI.23-23-08302.2003","article-title":"Metabotropic glutamate 5 receptor blockade alleviates akinesia by normalizing activity of selective basal\u2010ganglia structures in parkinsonian rats","volume":"23","author":"Breysse N.","year":"2003","journal-title":"J. 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