Serotonin and dopamine: unifying affective, activational, and decision functions.

Cools, Roshan; Nakamura, Kae; Daw, Nathaniel D

doi:10.1038/npp.2010.121

Cited by 464Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesNeuroscience and Neuropharmacology Research

Serotonin and dopamine: unifying affective, activational, and decision functions.

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Cools, Roshan, Nakamura, Kae, Daw, Nathaniel D·2011·Neuropsychopharmacology

DOI 10.1038/npp.2010.121PMC PMC3055512

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Abstract

Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotonin-comprising both affective and activational ones, as well as a number of other functions not overtly related to either-can be seen as consequences of a single root mechanism.

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Other neurotransmitters (serotonin, oxytocin, norepinephrine) appear to fulfill similar functions in regulating motivation in different motivational domains, such as withdrawal, contentment, affiliation, neural toning down, and curiosity.
“Other neurotransmitters (serotonin, oxytocin, norepinephrine) appear to fulfill similar functions in regulating motivation in different motivational domains, such as those of withdrawal, contentment, affiliation, neural toning down, and curiosity (e.g., Tops et al., 2009; Cools et al., 2010; Jepma et al., 2010; Veening et al., 2010; Lewis, 2011; Murphy et al., 2011).”
From Impulsive action: emotional impulses and their control (2014) · cites this paper as Cools et al., 2010
The sections on serotonin, aversive processing, and behavioral inhibition, and on the coupling between serotonin’s inhibitory and aversive effects, support a role for serotonin in regulating motivated responding. The cited paper does not establish the sentence’s broader claims about oxytocin, norepinephrine, or the full list of motivational domains. No page numbers are available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Drastic reduction of midbrain dopamine (in for instance Parkinson's disease) renders the patient passive and unresponsive, and peaks in dopamine by contrast reflect enhanced motivation or craving.
“Drastic reduction of midbrain dopamine (in for instance Parkinson’s disease) renders the patient passive and unresponsive, and peaks in dopamine by contrast reflect enhanced motivation (e.g., Cools et al., 2010; Aarts et al., 2012) or craving (Lewis, 2011).”
From Impulsive action: emotional impulses and their control (2014) · cites this paper as Cools et al., 2010
In “DA, REINFORCEMENT, AND BEHAVIORAL ACTIVATION” (page unavailable), the paper links dopaminergic degeneration in Parkinson’s disease to poverty of movement and describes dopamine as promoting behavioral vigor and incentive motivation. It does not say that patients become generally unresponsive or that dopamine peaks specifically reflect heightened motivation. The citing sentence attributes craving to Lewis (2011), not to this paper. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Neurons in MBD nuclei encode reward prediction errors.
“Neurons in MBD nuclei are believed to encode reward prediction errors (RPEs).45”
From Two prefrontal-subcortical circuits estimate controllability and reflect its impact on learning (2026) · cites this paper as [47]

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Deficits in Impulse Control Associated with Tonically-elevated Serotonergic Function in Rat Prefrontal Cortex
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Relationship between reward-enhancing and stereotypical effects of psychomotor stimulant drugs
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Brain Regional α-[11C]Methyl- l -Tryptophan Trapping in Impulsive Subjects With Borderline Personality Disorder
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Effects of central 5-hydroxytryptamine depletion on sensitivity to delayed and probabilistic reinforcement
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Tryptophan depletion reduces right inferior prefrontal activation during response inhibition in fast, event-related fMRI
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Effect of tryptophan depletion on impulsive behavior in men with or without a family history of alcoholism
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Central serotonin depletion impairs both the acquisition and performance of a symmetrically reinforced go/no-go conditional visual discrimination
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Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibility
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“Thus, as is the case for DA, 5-HT might have distinct effects in the ventral striatum, the amygdala, and the OFC (Clarke et al, 2008; Boulougouris and Robbins, 2010), or on functions associated with ventral versus dorsal frontostriatal circuitry (Tanaka et al, 2007).”
Background
SOME BEHAVIORAL EFFECTS OF SEROTONIN DEPLETION DEPEND ON METHOD: A COMPARISON OF 5,7‐DIHYDROXYTRYPTAMINE, p‐CHLOROPHENYLALANINE, p‐CHLOROAMPHETAMINE, AND ELECTROLYTIC RAPHE LESIONS*
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Houk J, Adams J, Barto A (1995). A model of how the basal ganglia generate and predict reinforcement. In: Houk J, Davis J, Beiser D (eds). Models Processing in the Basal Ganglia. MIT Press: Cambridge, MA. pp 249-270.

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Authors: Cools, R., Nakamura, K., & Daw, N. D.
Affiliations: Radboud University Nijmegen (NL)
Kansai Medical University (JP)
New York University (US)
Corresponding author: Cools, Roshan
ORCID: Cools, Roshan
Nakamura, Kae
Daw, Nathaniel D
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2010-08-25
Volume: 36
Issue: 1
Pages: 98-113
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/npp.2010.121
PMC: PMC3055512
OpenAlex: W2009480086
Cited by: 464
References: 182
Citations by year: 2026: 29 · 2025: 26 · 2024: 19 · 2023: 16 · 2022: 26 · 2021: 25 · 2020: 27 · 2019: 32 · 2018: 41 · 2017: 27 · 2016: 34 · 2015: 29 · 2014: 38 · 2013: 43 · 2012: 29
FWCI: 2.71
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Funders: McKnight Foundation
National Alliance for Research on Schizophrenia and Depression
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
National Institutes of Health
National Institute of Mental Health (R01MH087882)
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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: serotonin, dopamine, neuromodulation, decision-making, reinforcement learning, emotional functioning, adaptive behavior
MeSH terms: Affect, Animals, Avoidance Learning, Brain, Brain Chemistry, Decision Making, Dopamine, Humans, Models, Neurological, Motivation, Reward, Serotonin

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Serotonin and dopamine: unifying affective, activational, and decision functions.

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