QUANTITATIVE ASSESSMENT OF QUINOLINIC ACID-INDUCED STRIATAL TOXICITY IN RATS USING RADIOLIGAND BINDING ASSAYS

To validate specific, sensitive and quantitative markers of the rat mo del 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-labelle d D1 and [H-3]sulpiride-labelled D2 dopamine receptors, [H-3]CGS 21680 -labelled adenosine A2 receptors, [H-3]GBR 12935-labelled dopamine upt ake 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-methy l-D-aspartate receptor, to assess the non-N-methyl-D-aspartate-mediate d toxicity of quinolinic acid, and 31 pretreated with MK-801 plus scop olamine, an anticholinergic drug that prevents MK-801 neuronal toxicit y, [H-3]MK-801 and [H-3]PK 11195 are sensitive markers of quinolinic a cid toxicity. In addition, [H-3]SCH 23390, [H-3]CGS 21680 and [H-3]hem icholinium-3, are found to be specific markers of quinolinic acid-indu ced 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 an d [H-3]hemicholinium-3, suggesting that quinolinic acid may act by mec hanisms other than direct activation of N-methyl-D-aspartate receptors . Combined pretreatment with MK-801 and scopolamine increased the prot ection against quinolinic acid, suggesting an involvement of the choli nergic system.