Cognitive flexibility deficits in rats with dorsomedial striatal 6-hydroxydopamine lesions tested using a three-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.

Behavioral and Cytological Differences between Two Parkinson’s Disease Experimental Models

“…It is well known that rats with both MFB 6-OHDA lesions have postural instability and little ability to preserve equilibrium after tasks with destabilizing forces. Similarly, spontaneous movements are significantly altered [43]; this has not been reported after the unilateral 6-OHDA lesion.…”

A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model

“…TH immunostaining data were collected as previously reported and described quantitatively from lesioned and non-lesioned rats ( Wang et al, 2020 ). Rats were anesthetized, subjected to transcardial perfusion with ice-cold saline followed by ice-cold 4% PFA/PBS.…”

“…Selective sections spanning the 6-OHDA lesion in both the striatum and midbrain were subjected to TH-immunostaining using a primary antibody solution (1:2500 anti-tyrosine hydroxylase, Cat #AB152, Millipore-Sigma, Billerica, MA, USA), then visualized using a secondary antibody solution (1:5000 IRDye 800CW Goat anti-mouse Cat #926–3221, LI-COR, Lincoln, NE, USA). Images of tissues at the levels of the striatum representing the site of the 6-OHDA lesioning targeting the dmCPu and mid-ventral mesencephalon showing the midbrain dopaminergic neurons were obtained using a LI-COR Odyssey CLx (for internal landmarks, please see ( Wang et al, 2020 )).…”

“…We chose a 3-CSRT paradigm with an added rule reversal feature, called 3-CSRT-reversal (3-CSRT-R), to examine cognitive flexibility. Detailed methods are provided in our prior publication ( Wang et al, 2020 ). In brief, rats were food restricted and randomized to receive complex wheel exercise, simple wheel exercise, treadmill exercise, or no exercise.…”

“…Rats were trained to associate nose poking into an illuminated aperture with receiving a single sucrose pellet reward. Rats were familiarized with the test chamber and nose-poke and reward retrieval behavior were shaped in pretraining lasting 1 week as previously described ( Wang et al, 2020 ). Thereafter, during the regular phase of 3-CSRT training, the rats were trained following a progressive schedule with a fixed ratio 1 schedule response-reward task (up to 90 trials or 30 min each session per day, 5 days/week, 16 sessions).…”