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

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.

Caffeine promotes glutamate and histamine release in the posterior hypothalamus

“…Caffeine administration produced a large increase in waking, as reported in earlier studies (8,10,38). Waking was significantly (t ϭ 8.9, df 7, P Ͻ 0.0001, t-test) higher for 2 h post-caffeine …”

“…microdialysis; sleep; histamine; glutamate; caffeine CAFFEINE (1,3, is the most widely used waking stimulant. It produces an increase in waking and locomotor activity in rats (38). Caffeine has been demonstrated to reverse psychomotor impairments induced by alcohol, benzodiazepines, and antihistamines (10,24,25,30).…”

Comparison of simultaneous measurement of mouse locomotor activity by radiotelemetry and photobeam methods

“…blood pressure, heart rate or EEG changes (Gross, Milia, Plehm, Inagami, & Luft, 2000;Paterson, Wilson, Nutt, Hutson, & Ivarsson, 2009;Rinne, Harjunpää, Scheinin, & Savontaus, 2008). These measurements are often complemented with locomotor activity recordings.…”

Unexpected Occurrence of Caffeine in Sleep-Inducing Herbal Teas

“…[2] In cases of excessive consumption, disorientation, agitation or insomnia are frequently reported. [3,4] During a survey of more than 100 herbal dietary supplements, caffeine was often detected in slimming supplements but also in some linden-based sleep-aid phytopreparations. [5] Due to the antagonist properties of linden [6][7][8] (Tilia spp.)…”