Degeneration and RepairCognitive flexibility deficits in rats with dorsomedial striatal 6-hydroxydopamine lesions tested using a three-choice serial reaction time task with reversal learningWang, Zhuoa; Flores, Ilseb; Donahue, Erin K.b; Lundquist, Adam J.b; Guo, Yumeia; Petzinger, Giselle M.b,,c; Jakowec, Michael W.b,,c; Holschneider, Daniel P.a,,b,,c,,dAuthor Information aDepartment of Psychiatry and Behavioral Sciences, University of Southern California bGraduate Program in Neurosciences, University of Southern California Departments of cNeurology dBiomedical Engineering, University of Southern California, Los Angeles, California, USA Received 15 May 2020 Accepted 22 June 2020 Correspondence to Daniel P. Holschneider, MD, Department of Psychiatry and Behavioral Sciences, University of Southern California, 1975 Zonal Avenue, KAM 400, MC9037, Los Angeles, CA 90089-9037, USA, Tel: +1 323 442 1536; fax: +1 323 442 1587; e-mail: email@example.com NeuroReport: October 14, 2020 - Volume 31 - Issue 15 - p 1055-1064 doi: 10.1097/WNR.0000000000001509 Buy Metrics 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 6-hydroxydopamine 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 4 weeks 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 and interventions. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.