Guanfacine potentiates the activation of prefrontal cortex evoked by warning signals
Open accessAbstract
Background Warning signals evoke an alert state of readiness that prepares for a rapid response by priming a thalamo-frontal-striatal network that includes the dorsolateral prefrontal cortex (DLPFC). Animal models indicate that noradrenergic input is essential for this stimulus-driven activation of DLPFC, but the precise mechanisms involved have not been determined. We tested the role that postsynaptic alpha(2A) adrenoceptors play in the activation of DLPFC evoked by warning cues using a placebo-controlled challenge with the alpha(2A) agonist guanfacine. Methods Sixteen healthy young adults were scanned twice with event-related functional magnetic resonance imaging (fMRI), while performing a simple cued reaction time (RT) task following administration of a single dose of oral guanfacine (1 mg) and placebo in counterbalanced order. The RT task temporally segregates the neural effects of warning cues and motor responses and minimizes mnemonic demands. Results Warning cues produced a marked reduction in RT accompanied by significant activation in a distributed thalamo-frontal-striatal network, including bilateral DLPFC. Guanfacine selectively increased the cue-evoked activation of the left DLPFC and right anterior cerebellum, although this increase was not accompanied by further reductions in RT. The effects of guanfacine on DLPFC activation were specifically associated with the warning cue and were not seen for visual- or target-related activation. Conclusions Guanfacine produced marked increases in the cue-evoked activation of DLPFC that correspond to the well-described actions of postsynaptic alpha(2) adrenoceptor stimulation. The current procedures provide an opportunity to test postsynaptic alpha(2A) adrenoceptor function in the prefrontal cortex in the pathophysiology of several psychiatric disorders.
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Guanfacine activates dlPFC in human functional imaging studies.
“Guanfacine has also been shown to activate dlPFC in human functional imaging studies”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Clerkin et al., 2009
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- Authors
- Clerkin, S. M., Schulz, K. P., Halperin, J. M., Newcorn, J. H., Ivanov, I., Tang, C. Y., & Fan, J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Queens College, CUNY (US)
- Corresponding author
- Schulz, Kurt P.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 66
- Issue
- 4
- Pages
- 307-312
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC12858091
- OpenAlex
- W2137984696
- Cited by
- 28
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 3 · 2018: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institute of Mental Health (R21MH083164, K01MH070892)
- National Center for Research Resources (MO1RR00071, M01RR000071)
- 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
- guanfacine, alpha2A-adrenoceptor, noradrenergic system, dorsolateral prefrontal cortex, warning signs, alertness, anterior cerebellum, reaction time
- MeSH terms
- Adult, Brain, Brain Mapping, Cues, Double-Blind Method, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Psychomotor Performance, Reaction Time, Guanfacine, Prefrontal Cortex, Receptors, Adrenergic, alpha-2, Adrenergic alpha-2 Receptor Agonists
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