Financiado en parte por Merck Sharp and Dohme
A translational, caffeine-induced model of onset insomnia in rats and healthy volunteers
Paterson LM, Wilson SJ, Nutt DJ, Hutson PH, Ivarsson M
Psychopharmacology · 40 citas
Etiquetas de revisión
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Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Merck Sharp and Dohme
Según 1 financiador declarado.
Publicación
- Publicado
- 2007-01-16 · Psychopharmacology (Berl) · vol. 191 · número 4 · págs. 943–950
- Editorial
- Springer Science+Business Media
- Citado
- 60 citas · más que el 93% de estudios similares · 4.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 40 trabajos
- Acceso
- De pago
- Áreas de investigación
- Sleep and related disorders · Sleep and Wakefulness Research · Circadian rhythm and melatonin
- Palabras clave
- insomnia, caffeine, sleep latency, zolpidem, trazodone, hypnotics, GABAergic mechanisms, serotonergic mechanisms, sleep disorders, subjective sleep quality
- MeSH
- animals, humans, rats, rats, sprague-dawley, sleep initiation and maintenance disorders, disease models, animal, trazodone, pyridines, caffeine, gaba agonists, hypnotics and sedatives, central nervous system stimulants, electroencephalography, electromyography, polysomnography, telemetry, cross-over studies, double-blind method, reproducibility of results, sleep, dose-response relationship, drug, reference values, adult, male, zolpidem, selective serotonin reuptake inhibitors
5 autores
- Louise M. Paterson🇬🇧University of Bristol
- Sue J. Wilson🇬🇧University of Bristol
- David Nutt🇬🇧 · autor de correspondenciaUniversity of Bristol
- Peter H. Hutson🇬🇧MSD (UK) Limited (United Kingdom)
- Magnus Ivarsson🇬🇧MSD (UK) Limited (United Kingdom)
Resumen
El texto original del estudio, en el idioma en que se publicó.
Rationale
Insomnia is a common and disabling complaint for which there is a need for improved treatments. Successful drug discovery relies on the use of appropriate animal models to assess likely outcome in the clinic.
Objectives
The purpose of this study was to develop a translational, caffeine-induced 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 sleep-promoting agents with different pharmacology, zolpidem and trazodone, which have GABA-ergic and serotonergic mechanisms, respectively.
Materials and methods
In 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, placebo-controlled, 4-week 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 Questionnaire.
Results
Caffeine caused a significant prolongation in objective SOL in rats and humans. This effect was sensitive to zolpidem and trazodone, both of which attenuated the caffeine-induced increase in SOL. Furthermore, both hypnotics restored the disruption in subjective measures of sleep onset caused by caffeine in volunteers.
Conclusions
This model therefore provides a promising paradigm in which we can study novel treatments for sleep disorders and an opportunity for direct comparison of results between rodents and humans.
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