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Dopamine, But Not Serotonin, Regulates Reversal Learning in the Marmoset Caudate Nucleus

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Clarke, Hannah F., Hill, Gemma J., Robbins, Trevor W., Roberts, Angela C.·2011·The Journal of Neuroscience

DOI 10.1523/jneurosci.5066-10.2011PMC PMC3083841

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Abstract

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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Authors: Clarke, H. F., Hill, G. J., Robbins, T. W., & Roberts, A. C.
Affiliations: University of Cambridge (GB)
Corresponding author: Clarke, Hannah F.
ORCID: Clarke, Hannah F.
Robbins, Trevor W.
Roberts, Angela C.
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
DOI: 10.1523/jneurosci.5066-10.2011
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: other-oa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
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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Dopamine, But Not Serotonin, Regulates Reversal Learning in the Marmoset Caudate Nucleus

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