Aged rhesus monkeys: Cognitive performance categorizations and preclinical drug testing
| Autor: | Patrick M. Callahan, David Blake, Wayne D. Beck, Alvin V. Terry, Marc Plagenhoef |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Aging Quinuclidines medicine.medical_specialty Drug Evaluation Preclinical Thiophenes Disease Audiology Partial agonist Article 03 medical and health sciences Cellular and Molecular Neuroscience Cognition 0302 clinical medicine Animals Medicine Cognitive Dysfunction Effects of sleep deprivation on cognitive performance Pathological Nootropic Agents Pharmacology Encenicline business.industry Macaca mulatta Memory Short-Term 030104 developmental biology Nicotinic agonist Drug development Female business 030217 neurology & neurosurgery |
| Zdroj: | Neuropharmacology |
| ISSN: | 0028-3908 |
| Popis: | Rodent models have facilitated major discoveries in neurobiology, however, the low success rate of novel medications in clinical trials have led to questions about their translational value in neuropsychiatric drug development research. For age-related disorders of cognition such as Alzheimer’ disease (AD) there is interest in moving beyond transgenic amyloid-β and/or tau-expressing rodent models and focusing more on natural aging and dissociating “healthy” from “pathological” aging to identify new therapeutic targets and treatments. In complex disorders such as AD, it can also be argued that animals with closer neurobiology to humans (e.g., nonhuman primates) should be employed more often particularly in the later phases of drug development. The purpose of the work described here was to evaluate the cognitive capabilities of rhesus monkeys across a wide range of ages in different delayed response tasks, a computerized delayed match to sample (DMTS) task and a manual delayed match to position (DMTP) task. Based on specific performance criteria and comparisons to younger subjects, the older subjects were generally less proficient, however, some performed as well as young subjects, while other aged subjects were markedly impaired. Accordingly, the older subjects could be categorized as aged “cognitively-unimpaired” or aged “cognitively-impaired” with a third group (aged-other) falling in between. Finally, as a proof of principle, we demonstrated using the DMTP task that aged cognitively-impaired monkeys are sensitive to the pro-cognitive effects of a nicotinic acetylcholine receptor (nAChR) partial agonist, encenicline, suggesting that nAChR ligands remain viable as potential treatments for age-related disorders of cognition. |
| Databáze: | OpenAIRE |
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