Cognitive Flexibility Deficits in Rats with Dorsomedial Striatal 6-OHDA Lesions Tested Using a 3-Choice Serial Reaction Time Task with Reversal Learning

Abstract

Lesions of the dorsomedial striatum elicit deficits in cognitive flexibility that are an early feature of Parkinson's disease (PD), and presumably reflect alterations in frontostriatal processing. The current study aimed to examine deficits in cognitive flexibility in rats with bilateral 6hydroxydopamine (6-OHDA) lesions in the dorsomedial striatum. While deficits in cognitive flexibility have previously been examined in rodent PD models using the cross-maze, T-maze, and a food-digging task, the current study is the first to examine such deficits using a 3-choice serial reaction time task (3-CSRT) with reversal learning (3-CSRT-R). Although the rate of acquisition in 3-CSRT was slower in lesioned compared to control rats, lesioned animals were able to acquire a level of accuracy comparable to that of control animals following 16 days of training. In contrast, substantial and persistent deficits were apparent during the reversal learning phase. Our results demonstrate that deficits in cognitive flexibility can be robustly unmasked by reversal learning in the 3-CSRT-R paradigm, which can be a useful test for evaluating effects of dorsomedial striatal deafferentation.

Cognitive flexibility deficits in rats with dorsomedial striatal 6-hydroxydopamine lesions tested using a three-choice serial reaction time task with reversal learning

“…The copyright holder for this preprint (which this version posted April 9, 2020. ; https://doi.org/10.1101/2020.04.08.022269 doi: bioRxiv preprint test cognitive flexibility in rats with 6-hydroxydopamine (6-OHDA) lesion to the bilateral dorsomedial striatum. Whereas past research has generally used lever press in the 5-CSRT, it has been shown that nose poke is an easier response to learn in rats [9]. We therefore chose nose poke, which has been used in more recent 5-CSRT studies [6,7].…”