ArticleBiological psychiatry global open science2023
Dose-Dependent Dissociation of Pro-cognitive Effects of Donepezil on Attention and Cognitive Flexibility in Rhesus Monkeys.
Article in Biological psychiatry global open science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Cognitive engagement induces area-specific fingerprints of dopamine, acetylcholine, serotonin, glutamate and GABA in prefrontal cortex and striatum.bioRxiv : the preprint server for biology · 2026Article
- Assessing attentiveness and cognitive engagement across tasks using video-based action understanding in non-human primates.Journal of neuroscience methods · 2025Article
- Real-Time In Vivo Monitoring of Cholinergic Neurotransmission in the Mouse Brain Using a Microelectrochemical Choline Biosensor.The European journal of neuroscience · 2025Article
- Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation.Nature nanotechnology · 2025Article
- Differential cognitive enhancer effects of acetylcholinesterase inhibitors and memantine on age-related deficits in vigilance and sustained attention: a preclinical validation study.Behavioral and brain functions : BBF · 2025Article
- Evaluation of Attention Concentration in Sexually Mature Male Rhesus Monkeys (Macaca mulatta) and Hamadryas Baboons (Papio hamadryas).Bulletin of experimental biology and medicine · 2025Article
- A Multi-task Platform for Profiling Cognitive and Motivational Constructs in Humans and Nonhuman Primates.bioRxiv : the preprint server for biology · 2023Article
- Acoustomechanically activatable liposomes for ultrasonic drug uncaging.bioRxiv : the preprint server for biology · 2023Article
- MProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Solid-phase microextraction of endogenous metabolites from intact tissue validated using a Biocrates standard reference method kit.Journal of pharmaceutical analysis · 2023Article
- Solid-phase microextraction: a fit-for-purpose technique in biomedical analysis.Analytical and bioanalytical chemistry · 2022Article
- The Basal Forebrain Cholinergic Nuclei and Their Relevance to Schizophrenia and Other Psychotic Disorders.Frontiers in psychiatry · 2022Review
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Authors and funding
8 authors.
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Abstract
Background: Donepezil exerts pro-cognitive effects by nonselectively enhancing acetylcholine (ACh) across multiple brain systems. Two brain systems that mediate pro-cognitive effects of attentional control and cognitive flexibility are the prefrontal cortex and the anterior striatum, which have different pharmacokinetic sensitivities to ACh modulation. We speculated that these area-specific ACh profiles lead to distinct optimal dose ranges for donepezil to enhance the cognitive domains of attention and flexible learning. Methods: To test for dose-specific effects of donepezil on different cognitive domains, we devised a multitask paradigm for nonhuman primates that assessed attention and cognitive flexibility. The nonhuman primates received either vehicle or variable doses of donepezil before task performance. We measured intracerebral donepezil and its strength in preventing the breakdown of ACh within the prefrontal cortex and anterior striatum using solid phase microextraction neurochemistry. Results: The highest administered donepezil dose improved attention and made the subjects more robust against distractor interference, but it did not improve flexible learning. In contrast, only a lower dose range of donepezil improved flexible learning and reduced perseveration, but without distractor-dependent attentional improvement. Neurochemical measurements confirmed a dose-dependent increase of extracellular donepezil and decreases in choline within the prefrontal cortex and the striatum. Conclusions: The donepezil dose for maximally improving attention differed from the dose range that enhanced cognitive flexibility despite the availability of the drug in two major brain systems supporting these functions. These results suggest that in our cohort of adult monkeys, donepezil traded improvements in attention for improvements in cognitive flexibility at a given dose range.
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