The DOI matches its Crossref record; 107 of the 108 references it cites were found in a registry or an index.
The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“DA acts as an inverted U-shaped pattern to cognitive performance. As is reported, too lower or higher DA level elicited by clinically-inappropriate doses of d-amphetamine impairs cognition (12).”
From Effects of Lisdexamfetamine, a Prodrug of D-Amphetamine, on Locomotion, Spatial Cognitive Processing and Neurochemical Profiles in Rats: A Comparison With Immediate-Release Amphetamine (2022) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The cognitive-enhancing effects of amphetamine occur through the dopaminergic transmission activation which, in turn, is mediated by both D1 dopamine receptors and α2-adrenoceptors in postsynaptic neurons in PFC [188].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [188]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A psychomotor stimulant theory of addiction.
Wise, R. A., & Bozarth, M. A. (1987) · Psychological Review · doi:10.1037/0033-295x.94.4.469 · Cited by 2,747
Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes
Castellanos, F. X., & Tannock, R. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn896 · Cited by 1,827 · cited 1×
“As part of this, the PFC extends topographically organized projections to the striatum (61,62), a region that plays a prominent role in cognitive processes historically associated with the PFC and dysregulation of frontostriatal circuitry is implicated in ADHD (20).”
Balleine, B. W., & O'Doherty, J. P. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.131 · Cited by 1,775
Kelly, P. H., Seviour, P. W., & Iversen, S. D. (1975) · Brain Research · doi:10.1016/0006-8993(75)90233-4 · Cited by 1,740
Differential projections of the infralimbic and prelimbic cortex in the rat
Vertes, R. P. (2004) · Synapse · doi:10.1002/syn.10279 · Cited by 1,550
Medial Frontal Cortex Mediates Perceptual Attentional Set Shifting in the Rat
Birrell, J. M., & Brown, V. J. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04320.2000 · Cited by 1,421
The Role of the Dorsal Striatum in Reward and Decision-Making: Figure 1.
Balleine, B. W., Delgado, M. R., & Hikosaka, O. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1554-07.2007 · Cited by 1,390
Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates
Dalley, J. W., Cardinal, R. N., & Robbins, T. W. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.09.006 · Cited by 1,329
Prefrontal cortex in the rat: Projections to subcortical autonomic, motor, and limbic centers
Gabbott, P. L. A., Warner, T. A., Jays, P. R. L., Salway, P., & Busby, S. J. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20738 · Cited by 1,227
Bymaster, F. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(02)00346-9 · Cited by 1,123
Research works printed but not linked: 1
- 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.
Cited by
Sorted by citations
Dopamine promotes cognitive effort by biasing the benefits versus costs of cognitive work
Westbrook, A., van den Bosch, R., Määttä, J. I., Hofmans, L., Papadopetraki, D., Cools, R., & Frank, M. J. (2020) · Science · doi:10.1126/science.aaz5891 · Cited by 379
Dopamine Does Double Duty in Motivating Cognitive Effort
Westbrook, A., & Braver, T. S. (2016) · Neuron · doi:10.1016/j.neuron.2015.12.029 · Cited by 331
Xing, B., Li, Y.-C., & Gao, W.-J. (2016) · Brain Research · doi:10.1016/j.brainres.2016.01.005 · Cited by 196
The Use and Impact of Cognitive Enhancers among University Students: A Systematic Review
Sharif, S., Guirguis, A., Fergus, S., & Schifano, F. (2021) · Brain Sciences · doi:10.3390/brainsci11030355 · Cited by 170
Characterizing Attention with Predictive Network Models
Rosenberg, M. D., Finn, E. S., Scheinost, D., Constable, R. T., & Chun, M. M. (2017) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2017.01.011 · Cited by 151
Metadata
- Authors
- Spencer, R. C., Devilbiss, D. M., & Berridge, C. W.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Berridge, Craig W.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 77
- Issue
- 11
- Pages
- 940-950
- ISSN
- 0006-3223 (ISSN-L)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
