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The Neuropsychopharmacology of Fronto-Executive Function: Monoaminergic Modulation
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We review the modulatory effects of the catecholamine neurotransmitters noradrenaline and dopamine on prefrontal cortical function. The effects of pharmacologic manipulations of these systems, sometimes in comparison with the indoleamine serotonin (5-HT), on performance on a variety of tasks that tap working memory, attentional-set formation and shifting, reversal learning, and response inhibition are compared in rodents, nonhuman primates, and humans using, in a behavioral context, several techniques ranging from microiontophoresis and single-cell electrophysiological recording to pharmacologic functional magnetic resonance imaging. Dissociable effects of drugs and neurotoxins affecting these monoamine systems suggest new ways of conceptualizing state-dependent fronto-executive functions, with implications for understanding the molecular genetic basis of mental illness and its treatment.
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“Dopamine modulates motivation and reinforcement learning; norepinephrine regulates arousal and vigilance; serotonin contributes to impulse control and mood stabilization; acetylcholine enhances attention and memory encoding (Robbins and Arnsten, 2009).”
From Enhancement of modern defense capabilities by convergence of cognitive neuroscience and artificial intelligence (2026) · cites this paper as Robbins and Arnsten, 2009
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“Neurobiological mechanisms and neurotransmitter systems ranging from neurotransmitter regulation, like, dopamine, norepinephrine, serotonin, and acetylcholine to stress physiology related to hypothalamic-pituarity-adrenal axis or HPA axis and neural oscillations—provide the substrates for adaptability and resilience (Buzsáki, 2006; McEwen, 2007; Robbins and Arnsten, 2009).”
From Enhancement of modern defense capabilities by convergence of cognitive neuroscience and artificial intelligence (2026) · cites this paper as Robbins and Arnsten, 2009
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“Dopamine modulates motivation and reinforcement learning; norepinephrine regulates arousal and vigilance; serotonin contributes to impulse control and mood stabilization; acetylcholine enhances attention and memory encoding (Robbins and Arnsten, 2009).”
From Enhancement of modern defense capabilities by convergence of cognitive neuroscience and artificial intelligence (2026) · cites this paper as Robbins and Arnsten, 2009
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“monoaminergic modulation of the efficacy of synaptic connections in PFC circuits has profound effects on PFC-mediated executive function, including working memory, regulation of attention, inhibition of inappropriate behaviors, and impulsivity control 45.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [45]
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“Dopamine modulates motivation and reinforcement learning; norepinephrine regulates arousal and vigilance; serotonin contributes to impulse control and mood stabilization; acetylcholine enhances attention and memory encoding (Robbins and Arnsten, 2009).”
From Enhancement of modern defense capabilities by convergence of cognitive neuroscience and artificial intelligence (2026) · cites this paper as Robbins and Arnsten, 2009
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“In general, optimal levels of dopamine in PFC are essential for WM performance”
From Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits (2023) · cites this paper as Robbins & Arnsten, 2009
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“Dopamine modulates motivation and reinforcement learning; norepinephrine regulates arousal and vigilance; serotonin contributes to impulse control and mood stabilization; acetylcholine enhances attention and memory encoding (Robbins and Arnsten, 2009).”
From Enhancement of modern defense capabilities by convergence of cognitive neuroscience and artificial intelligence (2026) · cites this paper as Robbins and Arnsten, 2009
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“On the basis of animal models (Berridge et al, 2006;Robbins and Arnsten, 2009), the optimum alert state (see Figure 4) appears to be related to more moderate levels of activation of NE a-2A and DA D1 receptors in the PFC, but that stress-related increases of release of NE and DA and results in the activation of NE a-1 and b-1 receptor and excessive activation of D1 receptors (Arnsten, 2009).”
From Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress (2011) · cites this paper as Robbins and Arnsten, 2009
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“Research in adult human and animal models has suggested that intermediate levels of DA signaling in both PFC and striatum are necessary for optimal performance, following a Yerkes-Dodson inverted U-shaped dose response curve of DA signaling and behavior (Robbins and Arnsten 2009; Cools and D'Esposito 2011).”
From Developmental imaging genetics: Linking dopamine function to adolescent behavior (2014) · cites this paper as Robbins and Arnsten 2009
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Metadata
- Authors
- Robbins, T. W., & Arnsten, A. F. T.
- Affiliations
- University of Cambridge (GB)
- Yale University (US)
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2009-06-01
- Volume
- 32
- Issue
- 1
- Pages
- 267-287
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- PMC
- PMC2863127
- OpenAlex
- W2160985876
- Cited by
- 957
- References
- 143
- Citations by year
- 2026: 37 · 2025: 45 · 2024: 38 · 2023: 66 · 2022: 41 · 2021: 41 · 2020: 47 · 2019: 48 · 2018: 58 · 2017: 64 · 2016: 64 · 2015: 70 · 2014: 53 · 2013: 90 · 2012: 72
- FWCI
- 5.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- National Alliance for Research on Schizophrenia and Depression
- Wellcome Trust
- Medical Research Council
- National Institute on Alcohol Abuse and Alcoholism (RL1AA017536)
- National Institute on Aging (R37AG006036, P01AG030004, R01AG006036, AG06036)
- National Institute of Mental Health (P50MH068789)
- National Center for Research Resources (U54RR024350)
- 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
- norepinephrine, dopamine, serotonin, prefrontal cortex, working memory, set-shifting, reversal learning, response inhibition, neuropsychopharmacology, neurotoxins, mental illness
- MeSH terms
- Animals, Catecholamines, Cognition, Humans, Mental Processes, Synaptic Transmission, Neuropharmacology, Psychomotor Performance, Serotonin, Prefrontal Cortex, Neurocognitive Disorders
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