Effect of caffeine and morphine on the developing pre-mature brain.

Apnea of pre-maturity is common, occurring in 85% of infants born less than 34 week gestation. Oral caffeine is the most frequent form of therapy, often in conjunction with the use of intubation and intermittent ventilation. Morphine is used to reduce the pain believed to be associated with the latter. Little information is available on the effects of caffeine, morphine or their combination, on the developing brain. We determined the effect of caffeine and morphine alone and in combination of cell death on the developing brain of the rat. Cell death, measured by Fluoro-jade B and activated caspase-3, was significantly increased at 12 and 24 hour post-caffeine injection (P < 0.05) in the cortex, caudate, nucleus accumbens, hypothalamus, hippocampus and superior colliculus. No alterations were seen following morphine injection alone. However, in the thalamus, the combination of caffeine and morphine did increase cell death to a significantly greater extent than caffeine alone. Further research is required to determine the long-term pathologic and functional effects of caffeine and the combination of caffeine and morphine on the developing immature brain.