Quantitative assessment of quinolinic acid-induced striatal toxicity in rats using radioligand binding assays
(1994) Neurological Research : a journal of progress in neurosurgery, neurology and neurosciences — Vol. 16, n° 3, p. 194-200 (1994)
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- 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 [H-3]MK-801-labelled N-methyl-D-aspartate receptors, [H-3]SCH 23390-labelled D1 and [H-3]sulpiride-labelled D2 dopamine receptors, [H-3]CGS 21680-labelled adenosine A2 receptors, [H-3]GBR 12935-labelled dopamine uptake sites, [H-3]hemicholinium-3-labelled high affinity choline uptake sites and [H-3]PK 11195-labelled glial cells, in 3 groups of rats: 1) lesioned only, 2) pretreated with MK-807, an antagonist of the N-methyl-D-aspartate receptor, to assess the non-N-methyl-D-aspartate-mediated toxicity of quinolinic acid, and 31 pretreated with MK-801 plus scopolamine, an anticholinergic drug that prevents MK-801 neuronal toxicity, [H-3]MK-801 and [H-3]PK 11195 are sensitive markers of quinolinic acid toxicity. In addition, [H-3]SCH 23390, [H-3]CGS 21680 and [H-3]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 [H-3]MK-801, [H-3]SCH 23390 and [H-3]CGS 21680 but failed to do so for [H-3]sulpride and [H-3]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.
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Levivier, M., Holemans, S., Togasaki, D. M., Maloteaux, J.-M., Brotchi, J., & Przedborski, S. (1994). Quantitative assessment of quinolinic acid-induced striatal toxicity in rats using radioligand binding assays. Neurological Research : a journal of progress in neurosurgery, neurology and neurosciences, 16(3), 194-200. https://doi.org/10.1080/01616412.1994.11740226 (Original work published 1994)