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Enhancement of sustained attention performance by the nicotinic acetylcholine receptor agonist ABT-418 in intact but not basal forebrain-lesioned rats
Abstract
Rationale Loss of telencephalic cholinergic projections has been postulated to contribute significantly to the cognitive decline associated with aging and dementia.Objective The effects of the nicotinic acetylcholine receptor agonist ABT-418, a potential therapeutic drug for the treatment of the age- and dementia-associated cognitive disorders, were tested in an animal model of the cortical cholinergic deafferentation-induced impairments in sustained attention.Methods Animals were trained in an operant task designed to test sustained attention performance. A partial loss of cortical cholinergic inputs was produced by infusions of 192 IgG-saporin into the basal forebrain. The effects of the systemic administration of ABT-418 (0.04, 0.13, 0.39 mg/kg) and the psychostimulant methylphenidate (0.2, 0.4, 0.8 mg/kg) were assessed.Results Compared with sham-lesioned animals, this lesion resulted in a decrease in the relative number of hits while the relative number of correct rejections remained unaffected. Administration of ABT-418 significantly improved the relative number of hits. Furthermore, this effect of ABT-418 interacted with the effects of the lesion. Unexpectedly, this interaction was based on a significant enhancement of the performance of sham-lesioned animals while no effects were found in 192 IgG-saporin-lesioned animals. Administration of methylphenidate did not affect performance.Conclusions While these data do not support the hypothesis that administration of ABT-418 attenuates the impairments in attentional performance that result from loss of cortical cholinergic inputs, they support previous notions about this drug's ability to enhance cognitive processes in intact subjects.
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“Furthermore, because the attentional impairment caused by cholinergic lesions are not restored by pharmacologically mimicking the contributions of the tonic component of cholinergic neurotransmission (see below; McGaughy et al, 1999), the consequences of the lesions can be primarily attributed to the absence of cholinergic transients.”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as McGaughy et al, 1999
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Metadata
- Authors
- McGaughy, J., Decker, M. W., & Sarter, M.
- Affiliations
- The Ohio State University (US)
- Abbott (United States) (US)
- Venue
- Psychopharmacology
- Published
- 1999-05-20
- Volume
- 144
- Issue
- 2
- Pages
- 175-182
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2040720776
- Cited by
- 128
- References
- 28
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 10 · 2013: 10 · 2012: 7
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- ABT-418, nicotinic agonists, sustained attention, cholinergic deafferentation, basal forebrain lesions, methylphenidate, cognitive enhancement, dementia, aging, cholinergic projections, attentional performance
- MeSH terms
- Central Nervous System Stimulants, Animals, Attention, Behavior, Animal, Isoxazoles, Male, Methylphenidate, Pyrrolidines, Rats, Inbred F344, Receptors, Nicotinic, Prosencephalon, Nootropic Agents, Rats
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 ›
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