QUINOLINIC ACID-INDUCED LESIONS OF THE RAT STRIATUM - QUANTITATIVE AUTORADIOGRAPHIC BINDING ASSESSMENT

Injection of the excitatory amino-acid analog quinolinic acid into the striatum of rats produces neuropathological and neurochemical alterat ions that are reminiscent of those observed in Huntington's disease. I n the present study, we evaluated quinolinic acid-induced striatal cha nges using quantitative autoradiographic binding assays for [H-3]MK-80 1-labeled NMDA receptors, [H-3]SCH 23390-labeled dopamine D-1 and [H-3 ]sulpiride-labeled dopamine D-2 receptors, [H-3]CGS 21680-labeled aden osine A(2a) receptors, [H-3]mazindol-labeled dopamine uptake sites, [H -3]hemicholinium-3-labeled high affinity choline uptake sites and [H-3 ]PK 11195-labeled peripheral-type benzodiazepine binding sites, as mar kers of different cellular populations of the striatum. We found that decrease in [H-3]MK 801 and [H-3]SCH 23390 binding, and increase in [H -3]PK 11195 binding were the most significant alterations induced by t he intrastriatal injection of quinolinic acid. Concentrations of [H-3] CGS 21680 and [H-3]hemicholinium-3 bindings were also decreased, howev er, to a lesser extent, and [H-3]sulpiride binding was not significant ly affected. Quinolinic acid also produced an increase in [H-3]mazindo l binding. We tested the specificity of the N-methyl-D-aspartate recep tor-mediated mechanism of quinolinic acid neurotoxicity using MK 801 p retreatment, an N-methyl-D-aspartate receptor antagonist, and it preve nted all quinolinic acid-induced binding changes. Because anticholiner gic drugs were proposed to prevent the neurotoxic side-effects of MK 8 01, we also tested the effect of scopolamine pretreatment and found th at it altered neither the neurotoxicity induced by quinolinic acid nor the neuroprotective effect of MK 801.