Time-course analysis and comparison of acute and chronic intrastriatal quinolinic acid administration on forelimb reaching deficits in the rat

Rats were trained to use a single forelimb for a food pellet retrieval task. During baseline testing all rats exhibited >90% use of a preferred limb for the task. Following baseline, rats were subjected to chronic administration (18 day) or acute injection of quinolinic acid (QUIN) or vehicle to the striatum contralateral to the preferred Limb. Rats were tested 48 h after insertion of chronic delivery probes or after acute injection and retested every 48 h over an 18-day period. Compared to vehicle, rats receiving chronic QUIN (7.6 nmol/h) exhibited an increase in the number of reach attempts required to meet task criteria. Chronic QUIN did not produce a significant change in latency to initiate the task or an increase in latency to complete the task. No rats exposed to chronic QUIN exhibited a switch in Limb preference for the task. Unlike animals exposed to chronic QUIN, a significant number of animals receiving acute QUIN injections switched to exclusive use of the ipsilateral (nonpreferred) Limb for the task. Quantitative histological analysis revealed no significant difference in lesion volume between acute and chronic lesion animals. These findings suggest that behavioral manifestations of histopathologically similar lesions may be vastly different depending on the methods used to produce these lesions, More specifically, the acute injection model resulted primarily in forelimb disuse, whereas the chronic model resulted in continued abnormal use of the affected limb. Understanding adaptive strategies used in these models may be particularly important when testing newly developed transgenic models of neurodegenerative diseases and the therapeutic potential of newly developed neuroprotectants. (C) 1999 Academic Press.