The Effects of Caffeine on Sleep and Maturational Markers in the Rat

Abstract

Adolescence is a critical period for brain maturation during which a massive reorganization of cortical connectivity takes place. In humans, slow wave activity (<4.5 Hz) during NREM sleep was proposed to reflect cortical maturation which relies on use-dependent processes. A stimulant like caffeine, whose consumption has recently increased especially in adolescents, is known to affect sleep wake regulation.The goal of this study was to establish a rat model allowing to assess the relationship between cortical maturation and sleep and to further investigate how these parameters are affected by caffeine consumption. To do so, we assessed sleep and markers of maturation by electrophysiological recordings, behavioral and structural readouts in the juvenile rat. Our results show that sleep slow wave activity follows a similar inverted U-shape trajectory as already known in humans. Caffeine treatment exerted short-term stimulating effects and altered the trajectory of slow wave activity. Moreover, caffeine affected behavioral and structural markers of maturation. Thus, caffeine consumption during a critical developmental period shows long lasting effects on sleep and brain maturation.

Cortical Development, Electroencephalogram Rhythms, and the Sleep/Wake Cycle

“…Of note, the SWA rebound is not immediately apparent around the end of second week, when slow waves first appear in the sleep EEG, most likely because of a ceiling effect due to their very high amplitude (32). Indeed, in rats (33), mice (34) and humans (35–37) SWA during development follows an inverted U-shape that is believed to reflect cortical synaptic changes, first increasing and peaking due to synaptogenesis, and then declining through adolescence into adulthood due to refinement and/or pruning of synaptic connections (33, 34, 38). …”

Sleep and Early Cortical Development

“…Recent work has shown that caffeine consumption in adolescent rats exerts short-term stimulating effects and can alter the developmental trajectory of SWA [10]. Moreover, caffeine alters behavioral and structural markers of maturation [10].…”

“…Moreover, caffeine alters behavioral and structural markers of maturation [10]. These caffeine-induced lasting morphological changes might be due to alterations in sleep regulatory processes, such that altering sleep-wake regulation by stimulants like caffeine may affect synaptic plasticity.…”

“…In contrast to humans though, animals (rat, cat, guinea pig) exhibit a decrease in wakefulness throughout the first 2 weeks of life and an increase thereafter [7]. Throughout human as well as animal pubertal development, sleep architecture changes are less pronounced and include an increase in wakefulness and a decrease in both non-REM and REM sleep [9, 10]. …”

“…Despite the presence of endogenous SCN rhythms in the mammalian fetus, newborn animals do not display circadian organization [31]. By about 4 weeks, rats predominantly sleep during the light period [10]. A circadian delay resembling that of human adolescents has been shown in rhesus macaques [32]; however, species with polyphasic sleep experience a phase advance in puberty that is accompanied by an increasing consolidation of sleep and wakefulness bouts [33].…”