Journal Article

Dorsal and ventral striatal dopamine D1 and D2 receptors differentially modulate distinct phases of serial visual reversal learning

Alsiö Johan, Boulos, Maria, McKenzie, Colin, Sala-Bayo Júlia, Zhukovsky, Peter, Mareschi Alexis, Nicholson, Janet, Dalley, Jeffrey W, Fiddian Leanne, Hervig, Mona E, Robbins, Trevor W, Nilsson Simon R O

2020

Overview

Impaired cognitive flexibility in visual reversal-learning tasks has been observed in a wide range of neurological and neuropsychiatric disorders. Although both human and animal studies have implicated striatal D2-like and D1-like receptors (D2R; D1R) in this form of flexibility, less is known about the contribution they make within distinct sub-regions of the striatum and the different phases of visual reversal learning. The present study investigated the involvement of D2R and D1R during the early (perseverative) phase of reversal learning as well as in the intermediate and late stages (new learning) after microinfusions of D2R and D1R antagonists into the nucleus accumbens core and shell (NAcC; NAcS), the anterior and posterior dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) on a touchscreen visual serial reversal-learning task. Reversal learning was improved after dopamine receptor blockade in the nucleus accumbens; the D1R antagonist, SCH23390, in the NAcS and the D2R antagonist, raclopride, in the NAcC selectively reduced early, perseverative errors. In contrast, reversal learning was impaired by D2R antagonism, but not D1R antagonism, in the dorsal striatum: raclopride increased errors in the intermediate phase after DMS infusions, and increased errors across phases after DLS infusions. These findings indicate that D1R and D2R modulate different stages of reversal learning through effects localised to different sub-regions of the striatum. Thus, deficits in behavioral flexibility observed in disorders linked to dopamine perturbations may be attributable to specific D1R and D2R dysfunction in distinct striatal sub-regions.

• Publisher: Nature Publishing Group
• Subject: Animal behavior / Caudate-putamen / Cognitive ability / Dopamine / Dopamine D1 receptors / Dopamine D2 receptors / Flexibility / Mental disorders / Neostriatum / Neurological diseases / Nucleus accumbens / Observational learning / Raclopride / Reversal learning / Serial reversal learning / Visual discrimination learning