Effects of theophylline on behavioral state development in the newborn rabbit

On Day 1 of life (Day 0 = birth), the sleep-wake behavioral states of rabbits were measured for 2 hr, after which half the animals received 10 mg/kg of theophylline by intubation (N = 16), whereas the remainder received normal saline (N = 17). Behavioral states were then measured on Days 2, 3, 5, 7, 15, 20, 30 and 40. Theophylline sharply reduced active sleep starting on Day 2 and continuing through Day 20. The development of quiet sleep was delayed for 10 days in the drug-treated group. Paralleling the loss of active sleep was a major increase in wake between Days 2 to 20. The drug also affected the intermediate states of sleep-wake transition and active-quiet sleep transition. The data raise major questions about the safety of a drug widely used in the newborn intensive care setting.