Consequences of quinolinic acid-induced lesions of the neostriatum and frontal neocortex in rats: Behaviour, neuroanatomy and neurochemistry

Abstract

<p>Animals with kainate- and ibotenate-induced lesions demonstrated significant nocturnal hyperactivity; however, no such effect was found in the quinolinate lesioned animals. Further, the hyperactivity in the kainate- and ibotenate-lesioned animals attenuated over prolonged testing. This study indicates that spontaneous nocturnal activity may not always be an adequate measure of striatal dysfunction. Secondly, the behavioural profile of rats with quinolinic acid-induced lesions of the medial striatum was characterized. The lesioned rats were found to be impaired in two tests of cognitive behaviour, the Morris Water Maze and the spontaneous alternation task, but were apparently unimpaired on a host of motor tests, thus strengthening the interpretation that the impairment demonstrated on the two cognitive tasks was indeed indicative of impaired visuospatial processing. The behavioural data also suggested that the lesioned animals showed impaired cognitive flexibility, and an inability to change learning strategies. Histological analysis revealed significant striatal degeneration seemingly in the absence of cortical degeneration, thus suggesting that lesions largely restricted to the medial striatum are sufficient to produce a behavioural impairment. Animals were found to be impaired in the Morris Water Maze, but were unimpaired on a number of motor tests. Histological analysis demonstrated the presence of marked cortical degeneration; interestingly, striking ventricular dilation was also present in most of these animals. The results were discussed in relation to the pathology of HD. Lastly, a morphometric study was performed on rats with chronic excitotoxin-induced striatal lesions. Degenerative changes were noted in the striatum, substantia nigra and thalamic nuclei, but no changes were found in the thalamus as a whole or the cortex. The negative cortical finding was supported by a neurochemical study of various neuropeptides in rats with chronic quinolinic acid-induced lesions of the medial striatum. (Abstract shortened by UMI.)</p>