Caffeine is commonly used clinically to treat apnoeas and unstable breathing associated with
premature birth.
Caffeine antagonizes
adenosine receptors and acts as an efficient
respiratory stimulant in neonates. Owing to its persistent effects on
adenosine receptor expression in the brain, neonatal
caffeine administration also has significant effects on maturation of the respiratory control system. However, since
adenosine receptors are critically involved in sleep regulation, and sleep also modulates breathing, we tested the hypothesis that neonatal
caffeine treatment disrupts regulation of sleep and breathing in the adult rat. Neonatal
caffeine treatment (15 mg kg(-1) day(-1)) was administered from postnatal days 3-12. At adulthood (8-10 weeks old), sleep and breathing were measured with a telemetry system and whole-body plethysmography respectively. In adult rats treated with
caffeine during the neonatal period, sleep time was reduced, sleep onset latency was increased, and non-rapid eye movement (non-REM) sleep was fragmented compared to controls. Ventilation at rest was higher in
caffeine-treated adult rats compared to controls across sleep/wake states. Hypercapnic ventilatory responses were significantly reduced in
caffeine-treated rats compared to control rats across sleep/wake states. Additional experiments in adult anaesthetized rats showed that at similar levels of arterial blood
gases, phrenic nerve activity was enhanced in
caffeine-treated rats. This study demonstrates that administration of
caffeine in the neonatal period alters respiratory control system activity in awake and sleeping rats, as well as in the anaesthetized rats, and also has persistent disrupting effects on sleep that are apparent in adult rats.