The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD)
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BACKGROUND: ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. While dopamine release is decreased in SHR prefrontal cortex, norepinephrine concentrations are elevated. The noradrenergic system appears to be hyperactive as a result of impaired alpha-2A adrenoceptor regulation. Thus, the present study tested behavioral effects of the centrally acting alpha-2A adrenoceptor agonist guanfacine on SHR behavior. METHODS: The present study tested behavioral effects of guanfacine at doses of 0.075, 0.15, 0.30 and 0.60 mg base/kg i.p. in both male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. RESULTS: The striking impulsiveness, overactivity, and reduced sustained attention during baseline conditions in the SHR improved by treatment with guanfacine. The most pronounced improvement in SHR behavior was seen following the two highest doses (0.3 and 0.6 mg/kg) of guanfacine when SHR behaviors virtually normalized. The positive effects of the drug were most marked towards the end of the session. CONCLUSION: The results indicate that guanfacine improved poor noradrenergic modulation of neuronal circuits that involve the frontal lobes in an animal model of ADHD. The present results support the beneficial effects of guanfacine on ADHD behavior reported clinically and experimentally in primate models of frontal function. It is likely that guanfacine improved prefrontal functions in the SHR. It cannot be concluded, however, that the effects of the drug are mediated solely by norepinephrine.
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Systemic administration of guanfacine improves attentional performance in a rat model of ADHD, Spontaneously Hypertensive rats.
“Systemic administration of guanfacine also improves attentional performance in a rat model of ADHD, Spontaneously Hypertensive rats”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Sagvolden, 2006
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- Authors
- Sagvolden
- Venue
- Behavioral and Brain Functions
- Published
- 2006
- Volume
- 2
- Issue
- 1
- Pages
- 41
- ISSN
- 1744-9081 (ISSN-L)
- PMC
- PMC1764416
- OpenAlex
- W2139127187
- Cited by
- 94
- References
- 6
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 6 · 2013: 1 · 2012: 3
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Behavioral and Brain Functions (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- guanfacine, attention deficit hyperactivity disorder, spontaneously hypertensive rats, overactivity, impulsivity, sustained attention, noradrenergic system, prefrontal cortex, norepinephrine, visual discrimination task, animal model of ADHD
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