Authors: Louise M Paterson Sue J Wilson David J Nutt Peter H Hutson Magnus Ivarsson
Publish Date: 2007/01/16
Volume: 191, Issue: 4, Pages: 943-950
Abstract
The purpose of this study was to develop a translational caffeineinduced model of insomnia in rats and healthy volunteers We used sleep onset latency SOL as a comparable sleep measure between the two species The model was validated by two effective sleeppromoting agents with different pharmacology zolpidem and trazodone which have GABAergic and serotonergic mechanisms respectivelyIn rats radiotelemetry transmitters with electroencephalogram and electromyogram electrodes were implanted for sleep recording Animals were administered with caffeine alone 10 mg/kg or in combination with zolpidem 10 mg/kg or trazodone 20 mg/kg or vehicle in crossover experiments Home polysomnography was performed in 12 healthy male volunteers in a randomised placebocontrolled 4week crossover study Subjects received placebo caffeine 150 mg or caffeine in combination with zolpidem 10 mg or trazodone 100 mg Subjective sleep effects in volunteers were assessed using the Leeds Sleep Evaluation QuestionnaireCaffeine caused a significant prolongation in objective SOL in rats and humans This effect was sensitive to zolpidem and trazodone both of which attenuated the caffeineinduced increase in SOL Furthermore both hypnotics restored the disruption in subjective measures of sleep onset caused by caffeine in volunteers
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