Neonatal caffeine persistently increases breathing across sleep‐wake states in freely‐behaving adult rats

Abstract

Neonatal caffeine, an adenosine receptor antagonist widely used to treat respiratory instabilities, is administered during a sensitive period of development and persistently modifies respiratory control in rats (Montandon et al., 2006, Ped Res). Since adenosine modulates breathing, especially during sleep, we tested the hypothesis that neonatal caffeine would modify the ventilatory pattern of adult rats across sleep-wake states. Newborn rats received caffeine (15 mg/mL) or water (control) each day from postnatal day 3–12. At adulthood, ventilatory activity and sleep-wake states were evaluated using whole-body plethysmography combined with an EEG/EMG telemetry system in freely-behaving adult male rats. During wakefulness, caffeine-treated rats presented higher tidal volume (by 25%, P=0.034), but less post-sigh apneas (by 28%, P=0.023) than in controls. During non-REM sleep, respiratory frequency was higher (by 18%, P=0.024), and apnea occurrence lower (by 44%, P=0.003), in caffeine than in control rats. However, tidal volume sensitivity to CO2 was strongly attenuated by neonatal caffeine during REM sleep (P<0.001). These results suggest that neonatal caffeine modulates the ventilatory pattern and reduces respiratory instabilities in a sleep-wake state-dependent manner. This work was funded by CIHR and G.M. was supported by the Foundation for the Research into Children’ disease.