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Title: Translational measures of the effects of insufficient sleep on cognition in the rat
Author: Loomis, Sally
ISNI:       0000 0004 8503 185X
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2019
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Insufficient sleep is highly prevalent and associated with deficits in functional wakefulness. Thus, a need remains for pre-clinical evaluation of sleep restriction to develop countermeasures for functional deficits. The overall aim of this thesis was to evaluate translational methods to assess the cognitive consequences of sleep loss in the rat. We first compared the effects of 11-h sleep restriction induced by three novel non-invasive protocols on attention using a Simple Response Latency task (SRLT). Wakefulness was enforced by cylinder rotation following a Constant, Decreasing or 'Weibull' (i.e., modelled on EEG-driven sleep restriction) protocols. While all protocols resulted in sleep loss and attentional deficits, differences in sleep recovery and functional alterations were identified, with the Decreasing and Weibull methods inducing attentional deficits similar to those observed in humans. Many behavioural tasks use food as a reward in rodents, thus we next assessed the interaction of food and sleep restriction. Food-restricted rats displayed resilience in SRLT performance to the effects of 11-h sleep restriction compared to ad libitum-fed rats. By contrast, motivation for food reward value was not altered in a progressive ratio task. We then evaluated the effects of pharmacological treatments to counteract the effects of 11-h sleep restriction. The drugs showed distinct pro-vigilant profiles, with caffeine and modafinil displaying beneficial effects on SRLT performance. A non-pharmacological counter-measure (naps) was unsuccessful in alleviating functional deficits induced by sleep loss. Finally, we applied oxygen amperometry, as a surrogate of neuroimaging, and measured oxygen consumption in the nucleus accumbens during the SRLT. However, data interpretation was limited due to throughput capabilities. Overall, the data indicated the sleep restriction methodologies provide a translational platform to develop novel pro-vigilant compounds that improve sustained attention. Careful choice of methodologies (i.e., sleep restriction protocols; reward) is important when studying functional deficits induced by sleep loss in rodents.
Supervisor: Winsky-Sommerer, Raphaelle ; Dijk, Derk-Jan Sponsor: Eli Lilly and Company
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral