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Neonatal caffeine exposure alters adenosine receptor control of locomotor activity in the developing rat
1Department of Psychology, University of Rochester, N.Y.
Insights
Neonatal caffeine exposure in rat pups delayed the stimulatory effect of caffeine on locomotor activity. This suggests early caffeine may alter central adenosine receptor development and control over movement.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Caffeine is commonly administered to premature infants to treat apnea.
- The long-term effects of neonatal caffeine exposure on brain development are not fully understood.
- An animal model is needed to study caffeine's impact during critical developmental periods.
Purpose of the Study:
- To develop and validate an animal model for neonatal caffeine exposure.
- To investigate the effects of early caffeine exposure on locomotor activity and its regulation by adenosine receptors.
- To determine if neonatal caffeine exposure alters the developmental trajectory of central nervous system responses.
Main Methods:
- Developed a rat pup model mimicking human infant caffeine exposure levels (5-15 mg/l serum).
- Administered loading and maintenance doses of caffeine orally to rat pups from day 2 to 6 of life.
- Measured spontaneous and challenged locomotor activity in pups aged 12-28 days using adenosine receptor agonists and antagonists.
Main Results:
- Neonatal caffeine exposure did not alter baseline locomotor activity.
- The stimulatory effect of acute caffeine administration on locomotor activity was significantly delayed in neonatally exposed pups.
- Adenosine receptor agonist and antagonist challenges revealed altered responses in neonatally exposed pups.
Conclusions:
- Neonatal caffeine exposure delays the development of caffeine's stimulatory effects on locomotor activity.
- Early caffeine exposure may disrupt the maturation of central adenosine receptor systems regulating motor behavior.
- This animal model provides a platform for further research into the neurodevelopmental consequences of caffeine in preterm infants.
Abstract:
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.