Quinolinic acid released from polymeric brain implants causes behavioral and neuroanatomical alterations in a rodent model of Huntington's disease

Quinolinic acid (QA) is an N-methyl-D-aspartate agonist that has been shown to produce neurotoxic effects that mimic certain neurodegenerative disease s when administered to laboratory animals. Intrastriatal injections of QA i n rats have been used extensively to produce some of the neuropathological and behavioral deficits that are analogous to Huntington's disease (HD). Ho wever, acute intrastriatal injections of QA produce symptoms that are not a nalogous to the progressive nature of HD. Thus far, models using chronic ad ministration of QA that produce HD-like behavioral and neuroanatomical chan ges have necessitated the use of a relatively bulky and fragile microdialyt ic pump apparatus. The present study tested an alternative way of chronical ly administering QA. Specifically, this study tested whether gradual releas e of QA from ethylene vinylacetate (EVA) polymers could produce symptoms an alogous to HD. Rats received either no implants or bilateral intrastriatal implants of polymers with or without QA. Subsequent tests for spontaneous m otor activity (SMA), grip strength, balance, and learning ability in a radi al-arm-water-maze task revealed QA-induced impairments in balance and learn ing ability, but did not affect grip strength or SMA. Histological analysis revealed QA-induced enlargement of lateral ventricles, striatal atrophy, a nd striatal neuronal loss, with relative sparing of NADPH-diaphorase-positi ve neurons. These results suggest that QA released from polymers can produc e behavioral and neuropathological profiles analogous to early stages of HD and that EVA polymers offer a useful means of chronically delivering QA in rodent models of neurodegeneration. (C) 2000 Academic Press.