Long-Term Effect of a Single Dose of Caffeine on Sleep, the Sleep EEG and Neuronal Activity in the Peduncular Part of the Lateral Hypothalamus under Constant Dark Conditions

Background: Caffeine is a central nervous system stimulant that influences both the sleep–wake cycle and the circadian clock and is known to influence neuronal activity in the lateral hypothalamus, an important area involved in sleep–wake regulation. Light is a strong zeitgeber and it is known to interact with the effect of caffeine on the sleep–wake cycle. We therefore wanted to investigate the long-term effects of a single dose of caffeine under constant dark conditions. Methods: We performed long-term (2 days) electroencephalogram (EEG)/electromyogram recordings combined with multi-unit neuronal activity recordings in the peduncular part of the lateral hypothalamus (PLH) under constant darkness in Brown Norway rats, and investigated the effect of a single caffeine treatment (15 mg/kg) or saline control given 1 h after the onset of the endogenous rest phase. Results: After a reduction in sleep and an increase in waking and activity in the first hours after administration, also on the second recording day after caffeine administration, rapid eye movement (REM) sleep was still reduced. Analysis of the EEG showed that power density in the theta range during waking and REM sleep was increased for at least two days. Neuronal activity in PLH was also increased for two days after the treatment, particularly during non-rapid eye movement sleep. Conclusion: Surprisingly, the data reveal long-term effects of a single dose of caffeine on vigilance states, EEG, and neuronal activity in the PLH. The absence of a light–dark cycle may have enabled the expression of these long-term changes. It therefore may be that caffeine, or its metabolites, have a stronger and longer lasting influence, particularly on the expression of REM sleep, than acknowledged until now.