CoChat
Sign Up
Cited by 42Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsNeuroscience and Neuropharmacology Research

Reversal of visual attention dysfunction after AMPA lesions of the nucleus basalis magnocellularis (NBM) by the cholinesterase inhibitor donepezil and by a 5-HT1A receptor antagonist WAY 100635

Balducci, C., Nurra, M., Pietropoli, A., Samanin, R., Carli, M.·2003·Psychopharmacology
DOI 10.1007/s00213-002-1385-7
Open this paper in CoChat — free account

Abstract

Rationale Degeneration of the cholinergic magnocellular neurons in the basal forebrain and their cortical projections is a major feature of the neuropathology of Alzheimer's disease (AD). In addition to memory dysfunction, attentional functions are also impaired in AD.Objective We investigated the extent to which the cholinesterase inhibitor donepezil reversed the attentional performance deficit in nucleus basalis magnocellularis (NBM) lesioned rats. We also examined the effects of a selective and potent 5-HT(1A) receptor antagonist, WAY 100635, on the attentional deficit of NBM lesioned rats.Methods We injected alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the NBM to selectively destroy cholinergic neurons projecting to the neocortex. Attentional functions were examined using the 5-CSRT task, in which hungry rats were required to locate brief visual targets presented randomly in one of five locations in a specially designed chamber. RESULTS. AMPA lesions of the NBM caused marked reductions in choline acetyltransferase activity (ChAT) ranging from 30 to 46% in medial areas of the cortex (medial-frontal and cingulate) and from 58 to 72% in more lateral areas (anterior-dorso-lateral and parietal). AMPA lesioned rats made fewer correct responses (choice accuracy), longer latency to correct response and an increase in the number of premature and perseverative responses. These impairments showed some recovery over the next 12 weeks. Reducing the duration of the visual stimulus reinstated the impairments in choice accuracy. The anticholinesterase inhibitor donepezil at 1.0 mg/kg but not 0.5 mg/kg reversed the impairments in choice accuracy and correct response latency. The premature and perseverative over-responding of AMPA lesioned rats remained unchanged. A dose of 0.1 mg/kg WAY 100635 to AMPA-lesioned rats improved their choice accuracy but did not shorten correct response latencies. The number of premature responses was reduced by WAY 100635 but perseverative over-responding was not affected.Conclusions The attentional impairments induced due to cortical cholinergic dysfunction may be ameliorated by cholinergic treatments such as cholinesterase inhibitors. In addition, 5-HT(1A) receptors and the cortical cholinergic system exert balanced opposition in regulating attentional performance in the rat. Blockade of 5-HT(1A) receptors may be useful to treat some aspects of attentional dysfunction in AD.

Integrity signals

Registry

Crossref · 10.1007/s00213-002-1385-7

Cites

76 of 76 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Balducci, C., Nurra, M., Pietropoli, A., Samanin, R., & Carli, M.
Affiliations
Mario Negri Institute for Pharmacological Research (IT)
Corresponding author
Carli, M.
ORCID
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2003-03-05
Volume
167
Issue
1
Pages
28-36
ISSN
0033-3158 (ISSN-L)
DOI
10.1007/s00213-002-1385-7
OpenAlex
W2059771656
Cited by
42
References
76
Citations by year
2021: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2013: 2 · 2012: 5
FWCI
2.57
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Psychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
nucleus basalis magnocellularis, cholinergic neurons, cholinergic degeneration, Alzheimer's disease, attention deficits, donepezil, cholinesterase inhibitors, WAY-100635, 5-HT1A receptor antagonist, choline acetyltransferase, perseverative responding
MeSH terms
Donepezil, Acetylcholine, Animals, Attention, Cerebral Cortex, Cholinesterase Inhibitors, Dose-Response Relationship, Drug, Indans, Male, Photic Stimulation, Piperazines, Piperidines, Pyridines, Receptors, Serotonin, Serotonin Antagonists, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Excitatory Amino Acid Agonists, Basal Nucleus of Meynert, Receptors, Serotonin, 5-HT1, 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 ›

Are you an author, or do you see a problem with this page? Request a review