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

Abstract

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 nonhuman 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 sleepdisorder drugs at low cost and with less burden to animal subjects.

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

“…The importance of conducting long-term behavioral observations in a less constrained and more natural environment has also been recognized [ 60 ]. In our analysis, we employed the nano tag system to address these issues [ 61 , 62 ]. Despite its significant weight in relation to the mice, the nano tag successfully highlighted the hyperactive tendencies in Pcdh15 -null across 6 weeks in their home cages.…”

Sleep Disturbances and Depression Are Co-morbid Conditions: Insights From Animal Models, Especially Non-human Primate Model

“…In any way whatever, the research on animal models of sleep disorders provides a good clue and basis for clinical diagnosis and treatment of depression. NHPs are considered as a further valuable and translational animal model, which is necessary for sleep and related diseases ( 137 , 138 ). It is also an important entry point for increased efforts dedicated to collaborative translational endeavors.…”

Effect of chronic intermittent hypoxia on ocular and intraoral mechanical allodynia mediated via the calcitonin gene-related peptide in a rat

“…Nano-Tags (18.8 × 14.2 × 7.1 mm 3 , 2.7 g; Kissei Comtec Co. Ltd., Nagano, Japan) were implanted under the skin of the back under 3% isoflurane anesthesia more than 10 days before recording. Nano-Tag methodology identifies sleep–wake states in animals [ 38 ]. The locomotor activity was recorded every 30 seconds and stored in Nano-Tag, and the data were transferred to the Nano-Tag Viewer program (Kissei Comtec Co. Ltd.) percutaneously at 11:00 under light isoflurane anesthesia.…”