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Simplified drug efficacy screening system for sleep-disorder drugs using non-human primates

The most widely used animal models to develop sleep-disorder drugs are rodents, particularly rats and mice. However, unlike humans, these rodents are nocturnal. Thus, diurnal non-human primates represent a valuable and more translational animal model to study sleep. Although sleep-disorder drugs hav...

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Autores principales: Sakai, Keita, Ishikawa, Akiyoshi, Mizuno, Yuri, Maki, Takehiro, Oda, Yasuhiro, Takahashi, Eiki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058904/
https://www.ncbi.nlm.nih.gov/pubmed/32154428
http://dx.doi.org/10.1016/j.heliyon.2020.e03524
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author Sakai, Keita
Ishikawa, Akiyoshi
Mizuno, Yuri
Maki, Takehiro
Oda, Yasuhiro
Takahashi, Eiki
author_facet Sakai, Keita
Ishikawa, Akiyoshi
Mizuno, Yuri
Maki, Takehiro
Oda, Yasuhiro
Takahashi, Eiki
author_sort Sakai, Keita
collection PubMed
description The most widely used animal models to develop sleep-disorder drugs are rodents, particularly rats and mice. However, unlike humans, these rodents are nocturnal. Thus, diurnal non-human primates represent a valuable and more translational animal model to study sleep. Although sleep-disorder drugs have been screened in non-human primates, the use of a telemetry system is not a desirable method for a rapid drug efficacy assessment system because of the need for expensive equipment, complicated surgery, and the long time before results can be obtained from analysis by inspection. Locomotor activity has traditionally been used as an indicator of the effects of drugs, genes, and disease models. The Nano-Tag, a new device for analyzing activity after an easy implantation surgery, measures locomotor activity without expensive equipment and the need for inspection for data processing, and the overall cost is much lower than that of a telemetry system. In this study, we compared the data obtained from polysomnography and on locomotor activity in telemetry transmitter-embedded cynomolgus monkeys by implanting the Nano-Tag subcutaneously in the forehead and administering sleep-disorder drugs to confirm if sleep–wake states could be measured using the Nano-Tag. When we compared the changes in awake time per unit time measured using polysomnography and locomotor activity counts per unit time measured using the Nano-Tag, cynomolgus monkeys exhibited a diurnal preference, and the correlation coefficients were positive during the 24-h period. Additionally, the correlation coefficients during the 12-h dark period were positive when the hypersomnia treatment drug modafinil was administered. The correlation coefficients during the 12-h light period were also positive when the insomnia treatment drug triazolam was administered. These results suggest that measuring locomotor activity is an effective tool for identifying sleep–wake states and screening sleep-disorder drugs at low cost and with less burden to animal subjects.
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spelling pubmed-70589042020-03-09 Simplified drug efficacy screening system for sleep-disorder drugs using non-human primates Sakai, Keita Ishikawa, Akiyoshi Mizuno, Yuri Maki, Takehiro Oda, Yasuhiro Takahashi, Eiki Heliyon Article The most widely used animal models to develop sleep-disorder drugs are rodents, particularly rats and mice. However, unlike humans, these rodents are nocturnal. Thus, diurnal non-human primates represent a valuable and more translational animal model to study sleep. Although sleep-disorder drugs have been screened in non-human primates, the use of a telemetry system is not a desirable method for a rapid drug efficacy assessment system because of the need for expensive equipment, complicated surgery, and the long time before results can be obtained from analysis by inspection. Locomotor activity has traditionally been used as an indicator of the effects of drugs, genes, and disease models. The Nano-Tag, a new device for analyzing activity after an easy implantation surgery, measures locomotor activity without expensive equipment and the need for inspection for data processing, and the overall cost is much lower than that of a telemetry system. In this study, we compared the data obtained from polysomnography and on locomotor activity in telemetry transmitter-embedded cynomolgus monkeys by implanting the Nano-Tag subcutaneously in the forehead and administering sleep-disorder drugs to confirm if sleep–wake states could be measured using the Nano-Tag. When we compared the changes in awake time per unit time measured using polysomnography and locomotor activity counts per unit time measured using the Nano-Tag, cynomolgus monkeys exhibited a diurnal preference, and the correlation coefficients were positive during the 24-h period. Additionally, the correlation coefficients during the 12-h dark period were positive when the hypersomnia treatment drug modafinil was administered. The correlation coefficients during the 12-h light period were also positive when the insomnia treatment drug triazolam was administered. These results suggest that measuring locomotor activity is an effective tool for identifying sleep–wake states and screening sleep-disorder drugs at low cost and with less burden to animal subjects. Elsevier 2020-03-04 /pmc/articles/PMC7058904/ /pubmed/32154428 http://dx.doi.org/10.1016/j.heliyon.2020.e03524 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sakai, Keita
Ishikawa, Akiyoshi
Mizuno, Yuri
Maki, Takehiro
Oda, Yasuhiro
Takahashi, Eiki
Simplified drug efficacy screening system for sleep-disorder drugs using non-human primates
title Simplified drug efficacy screening system for sleep-disorder drugs using non-human primates
title_full Simplified drug efficacy screening system for sleep-disorder drugs using non-human primates
title_fullStr Simplified drug efficacy screening system for sleep-disorder drugs using non-human primates
title_full_unstemmed Simplified drug efficacy screening system for sleep-disorder drugs using non-human primates
title_short Simplified drug efficacy screening system for sleep-disorder drugs using non-human primates
title_sort simplified drug efficacy screening system for sleep-disorder drugs using non-human primates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058904/
https://www.ncbi.nlm.nih.gov/pubmed/32154428
http://dx.doi.org/10.1016/j.heliyon.2020.e03524
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