Abstract
AbstractImpaired 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.
Funder
RCUK | Biotechnology and Biological Sciences Research Council
Lundbeckfonden
No personal funding for this project
Wellcome Trust
GlaxoSmithKline foundation
Shionogi
Publisher
Springer Science and Business Media LLC
Subject
Psychiatry and Mental health,Pharmacology
Reference58 articles.
1. Leeson VC, Robbins TW, Matheson E, Hutton SB, Ron MA, Barnes TRE, et al. Discrimination learning, reversal, and set-shifting in first-episode schizophrenia: stability over six years and specific associations with medication type and disorganization syndrome. Biol Psychiatry. 2009;66:586–93.
2. Remijnse PL, van den Heuvel OA, Nielen MMA, Vriend C, Hendriks GJ, Hoogendijk WJG, et al. Cognitive inflexibility in obsessive-compulsive disorder and major depression is associated with distinct neural correlates. PLoS ONE. 2013;8:e359600, 1–8.
3. Cools R, Barker Ra, Sahakian BJ, Robbins TW. Enhanced or impaired cognitive function in Parkinson’s disease as a function of dopaminergic medication and task demands. Cereb Cortex. 2001;11:1136–43.
4. Ersche KD, Roiser JP, Abbott S, Craig KJ, Mller U, Suckling J, et al. Response perseveration in stimulant dependence is associated with striatal dysfunction and can be ameliorated by a D2/3receptor agonist. Biol Psychiatry. 2011;70:754–62.
5. Lee B, Groman S, London ED, Jentsch JD. Dopamine D2/D3 receptors play a specific role in the reversal of a learned visual discrimination in monkeys. Neuropsychopharmacology. 2007;32:2125–34.
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