Cited by 164Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeuroethics, Human Enhancement, Biomedical Innovations

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The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex

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Spencer, Robert C., Devilbiss, David M., Berridge, Craig W.·2015·Biological Psychiatry

DOI 10.1016/j.biopsych.2014.09.013PMC PMC4377121

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Abstract

Psychostimulants are highly effective in the treatment of attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. In contrast, while the striatum is a critical participant in PFC-dependent cognition, where examined, psychostimulant action within the striatum is not sufficient to enhance cognition. At doses that moderately exceed the clinical range, psychostimulants appear to improve PFC-dependent attentional processes at the expense of other PFC-dependent processes (e.g., working memory, response inhibition). This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacologic treatments for attention-deficit/hyperactivity disorder and other conditions associated with PFC dysregulation.

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Spencer RC, Waterhouse BD, Berridge CW (in press): Neurocircuitry and receptor mechanisms underlying the differential sensitivity of prefrontal cognitive processes to psychostimulants. Soc Neurosci Abst.

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“As is reported, too lower or higher DA level elicited by clinicallyinappropriate doses of d-amphetamine impairs cognition (12).”
Background
A Dopamine D1 Agonist Versus Methylphenidate in Modulating Prefrontal Cortical Working Memory
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Authors: Spencer, R. C., Devilbiss, D. M., & Berridge, C. W.
Affiliations: University of Wisconsin–Madison (US)
Corresponding author: Berridge, Craig W.
ORCID: Spencer, Robert C.
Devilbiss, David M.
Berridge, Craig W.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2015-06
Volume: 77
Issue: 11
Pages: 940-950
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2014.09.013
PMC: PMC4377121
OpenAlex: W2080244900
Cited by: 164
References: 108
Citations by year: 2026: 7 · 2025: 13 · 2024: 8 · 2023: 15 · 2022: 18 · 2021: 22 · 2020: 9 · 2019: 20 · 2018: 13 · 2017: 17 · 2016: 14 · 2015: 8
FWCI: 1.80
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Rowan Digitals Works (Rowan University) (submittedVersion, cc-by-nc-nd)
Funders: Public Health Service (MH098631, MH081843, DA000389)
National Science Foundation (NSF 0918555)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Arts and Humanities › Philosophy › Neuroethics, Human Enhancement, Biomedical Innovations
Keywords: psychostimulants, cognitive enhancement, prefrontal cortex, attention deficit hyperactivity disorder, catecholamines, dopamine D1 receptor, striatum, frontostriatal circuits, dose-dependent effects, working memory, response inhibition, attention
MeSH terms: Central Nervous System Stimulants, Animals, Cognition, Humans, Prefrontal Cortex

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The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex

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