Neonatal caffeine exposure alters adenosine receptor control of locomotor activity in the developing rat.

An animal model was developed to approximate the magnitude and brain developmental period of caffeine exposure experienced by the human infant receiving caffeine for apnea of prematurity. Serum levels of caffeine of 5-15 mg/l over the 24-hour period were achieved by administering to rat pups a loading dose of 20 mg/kg p.o. on day 2, followed by 15 mg/kg p.o. on days 3-6 of life. Locomotor activity, both spontaneous and following an acute challenge with D-phenylisopropyl adenosine (an adenosine receptor agonist, 10 mumol/kg i.p.) or caffeine (an adenosine receptor antagonist, 100 mumol/kg i.p.), was measured in 12-to 28-day-old native rat pups or pups neonatally exposed to caffeine. The stimulatory effect of acute caffeine on locomotor activity was developmentally delayed in neonatally exposed pups. It is postulated that early exposure to caffeine in some way altered the development of the central adenosine receptor control over locomotor activity.