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Dopamine, But Not Serotonin, Regulates Reversal Learning in the Marmoset Caudate Nucleus
Open accessAbstract
Studies of visual discrimination reversal learning have revealed striking neurochemical dissociations at the level of the orbitofrontal cortex (OFC) with serotoninergic, but not dopaminergic, integrity being important for successful reversal learning. These findings have considerable implications for disorders such as obsessive compulsive disorder and schizophrenia, in which reversal learning is impaired, and which are primarily treated with drugs targeting the dopaminergic and serotoninergic systems. Dysfunction in such disorders however, is not limited to the OFC and extends subcortically to other structures implicated in reversal learning, such as the medial caudate nucleus. Therefore, because the roles of the serotonin and dopamine within the caudate nucleus are poorly understood, this study compared the effects of selective serotoninergic or selective dopaminergic depletions of the marmoset medial caudate nucleus on serial discrimination reversal learning. All monkeys were able to learn novel stimulus–reward associations but, unlike control monkeys and monkeys with selective serotoninergic medial caudate depletions, dopamine-depleted monkeys were markedly impaired in their ability to reverse this association. This impairment was not perseverative in nature. These findings are the opposite of those seen in the OFC and provide evidence for a neurochemical double dissociation between the OFC and medial caudate in the regulation of reversal learning. Although the specific contributions of these monoamines within the OFC–striatal circuit remain to be elucidated, these findings have profound implications for the development of drugs designed to remediate some of the cognitive processes underlying impaired reversal learning.
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“Depletion of dopamine in this brain region, but not in the OFC, caused deficits in marmosets (Clarke et al 2011, Clarke et al 2007)”
From Prefrontal cortex executive processes affected by stress in health and disease (2018) · cites this paper as Clarke et al 2011
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“and dopamine depletion in those brain areas impairs cognitive control (Clarke et al., 2011; Collins et al., 2000; Crofts et al., 2001; O'Neill and Brown, 2007).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Clarke et al., 2011
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Metadata
- Authors
- Clarke, H. F., Hill, G. J., Robbins, T. W., & Roberts, A. C.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Clarke, Hannah F.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-16
- Volume
- 31
- Issue
- 11
- Pages
- 4290-4297
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3083841
- OpenAlex
- W1966180070
- Cited by
- 144
- References
- 94
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 3 · 2022: 9 · 2021: 13 · 2020: 13 · 2019: 12 · 2018: 7 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 16 · 2013: 13 · 2012: 7
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- James S. McDonnell Foundation
- Wellcome Trust (75491, 076274/Z/04/Z, 093875)
- University of Cambridge
- Medical Research Council
- Newnham College, University of Cambridge
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- reversal learning, dopamine, serotonin, marmoset, orbitofrontal cortex, perseveration, obsessive-compulsive disorder, schizophrenia, cognitive impairment
- MeSH terms
- Analysis of Variance, Animals, Callithrix, Caudate Nucleus, Chromatography, High Pressure Liquid, Discrimination Learning, Dopamine, Female, Male, Photic Stimulation, Reversal Learning, Reward, Serotonin, Visual Perception
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