title: Quantitative assessment of quinolinic acid-induced striatal toxicity in rats using radioligand binding assays.
abstract: To validate specific, sensitive and quantitative markers of the rat model of Huntington's disease produced by the intrastriatal injection of quinolinic acid, we used striatal homogenate binding assays for [3H]MK-801-labelled N-methyl-D-aspartate receptors, [3H]SCH 23390-labelled D1 and [3H]sulpiride-labelled D2 dopamine receptors, [3H]CGS 21680-labelled adenosine A2 receptors, [3H]GBR 12935-labelled dopamine uptake sites, [3H]hemicholinium-3-labelled high affinity choline uptake sites and [3H]PK 11195-labelled glial cells, in 3 groups of rats: 1) lesioned only, 2) pretreated with MK-801, an antagonist of the N-methyl-D-aspartate receptor, to assess the non-N-methyl-D-aspartate-mediated toxicity of quinolinic acid, and 3) pretreated with MK-801 plus scopolamine, an anticholinergic drug that prevents MK-801 neuronal toxicity. [3H]MK-801 and [3H]PK 11195 are sensitive markers of quinolinic acid toxicity. In addition, [3H]SCH 23390, [3H]CGS 21680 and [3H]hemicholinium-3, are found to be specific markers of quinolinic acid-induced toxicity on striatonigral and striatopallidal projecting neurons, and on large interneurons, respectively. MK-801 pretreatment prevented the quinolinic acid-induced reduction in binding of [3H]MK-801, [3H]SCH 23390 and [3H]CGS 21680 but failed to do so for [3H]sulpride and [3H]hemicholinium-3, suggesting that quinolinic acid may act by mechanisms other than direct activation of N-methyl-D-aspartate receptors. Combined pretreatment with MK-801 and scopolamine increased the protection against quinolinic acid, suggesting an involvement of the cholinergic system.
authors.affiliation: Department of Neurosurgery, Université Libre de Bruxelles-Erasme Hospital, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Levivier
authors.forename: S
authors.initials: S
authors.lastname: Holemans
authors.forename: D M
authors.initials: DM
authors.lastname: Togasaki
authors.forename: J M
authors.initials: JM
authors.lastname: Maloteaux
authors.forename: J
authors.initials: J
authors.lastname: Brotchi
authors.forename: S
authors.initials: S
authors.lastname: Przedborski
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000473:pathology*; D009457:Neuroglia / Q000502:physiology; D017378:Quinolinic Acid / Q000633:toxicity*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D012601:Scopolamine; D017378:Quinolinic Acid