| Summary: | 碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 93 === Caffeine is used clinically to treat apnea in preterm infants. The brain developmental stage of preterm infants is usually at a period of rapid brain growth, referred as synaptogenesis, which occurs during early postnatal life in rats. In this period, the central nerve system (CNS) is highly sensitive to CNS acting drugs. In this study, we evaluated whether caffeine treatment during synaptogenesis produces any developmental and behavioral impairment. Since caffeine is an antagonist of the adenosine A1and A2A receptors, the adenosine receptor-related behaviors, such as analgesia (hot plate and tail flick test), anti-anxiety (elevated plus maze and dark-light transition test), learning and memory (step-through passive avoidance test and Morris water maze), hypothermia (rectal temperature) and hypolocomotion (locomotor activity) were examined. Sprague-Dawley rats administered either deionized water or caffeine (15-20 mg/kg/day) through gavage (0.05 ml/10 g) over postnatal days (PN) 2-6. The response latency in caffeine-exposed rats was significantly reduced in hot plate test but not in tail flick test. Caffeine-exposed rats showed less anxiety than control in the elevated plus maze and dark-light transition. In learning and memory test, caffeine-exposed rats showed impairment of memory retention in step through avoidance learning test but no differences in spatial learning ability in Morris water maze. Moreover, neonatal caffeine exposure increased adenosine receptor agonist-induced reduction in locomotion and rectal temperature compared with control rats. RT-PCR analysis demonstrated that adenosine receptor A2A subunit in the striatum of female rats was increased. However, western blot analysis showed the levels of adenosine A1 and A2a receptor was unaffected except A1 receptor expression increased in amygdala. These results indicate that neonatal caffeine exposure alters the adenosine receptor-related behaviors and the sensitivity to adenosine agonists, suggesting the risk may exist in preterm newborns treated for apnea with caffeine.
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