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Characterisation of the effects of caffeine on sleep in the rat: a potential model of sleep disruption

Psychopharmacology Unit, University of Bristol, Bristol, UK Louise.Paterson{at}bristol.ac.uk

SJ Wilson

Psychopharmacology Unit, University of Bristol, Bristol, UK

DJ Nutt

Psychopharmacology Unit, University of Bristol, Bristol, UK

PH Hutson

Address where research took place: Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Harlow, Essex, UK; Current address: Department of Schizophrenia Research, Merck & Co., Inc. West Point, PA, USA

M Ivarsson

Address where research took place: Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Harlow, Essex, UK; Current address: Pfizer Global Research and Development, Sandwich, Kent, UK

Abstract

Caffeine is known to disrupt sleep and its administration to human subjects has been used to model sleep disruption. We previously showed that its effects on sleep onset latency are comparable between rats and humans. This study evaluated the potential use of caffeine as a model of sleep disruption in the rat, by assessing its effects on sleep architecture and electroencephalogram (EEG) frequency spectrum, and using sleep-promoting drugs to reverse these effects. Rats were implanted with radiotelemetry devices for body temperature, EEG, electromyogram and locomotor activity. Following recovery, animals were dosed with caffeine (10 mg/kg) alone or in combination with zolpidem (10 mg/kg) or trazodone (20 mg/kg). Sleep was scored for the subsequent 12 h using automated analysis software. Caffeine dose-dependently disrupted sleep: it increased WAKE time, decreased NREM (non-REM) sleep time and NREM bout duration (but not bout number), and decreased delta activity in NREM sleep. It also dose-dependently increased locomotor activity and body temperature. When given alone, zolpidem suppressed REM whilst trazodone increased NREM sleep time at the expense of WAKE, increased NREM bout duration, increased delta activity in NREM sleep and reduced body temperature. In combination, zolpidem attenuated caffeine’s effects on WAKE, whilst trazodone attenuated its effects on NREM sleep, NREM bout duration, delta activity, body temperature and locomotor activity. Caffeine administration produced many of the signs of insomnia that were improved by two of its most successful current treatments. This model may therefore be useful in the study of new drugs for the treatment of sleep disturbance.

Key Words: 5-HT • caffeine • EEG • insomnia • rat • sleep • telemetry • trazodone • zolpidem

This version was published on July 1, 2009

Journal of Psychopharmacology, Vol. 23, No. 5, 475-486 (2009)
DOI: 10.1177/0269881109104846


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