Fisher S, Guillet R
Department of Pediatrics (Neonatology), Children's Hospital at Strong, University of Rochester, School of Medicine and Dentistry, NY 14642, USA.
Brain Res Dev Brain Res. 1997 Jan 2;98(1):145-9. doi: 10.1016/s0165-3806(96)00158-7.
Chronic administration of an adenosine receptor antagonist disturbs spatial learning and memory in adult mice and neonatal caffeine exposure results in long-term behavioral and biochemical sequelae in mice and rats. We thus postulated that early treatment with caffeine would have latent effects on learning and memory as measured in a passive avoidance paradigm. Rats were not handled or received caffeine (15-20 mg/kg/day) by gavage over postnatal days 2-6. At 28 or 70-90 days of age, rats were trained to avoid an electrified grid and tested for retention 24 h, 72 h, and 7 days later. At 28 days, caffeine-exposed rats required more trials to meet criterion than did control rats, regardless of gender. There was minimal effect on retention of either neonatal treatment or gender at this age. At 70-90 days, there was no effect of either gender or treatment on learning; however, there was a significant effect of gender (P < 0.05) on retention at 24 h that was more pronounced in neonatally caffeine-treated rats (P < 0.01). At 72 h, the effect of caffeine on retention differed between male and female rats. Neonatal caffeine exposure significantly improved retention in females (P < 0.01) and significantly decreased retention in males (P < 0.05). Thus, caffeine exposure limited to the first week of life resulted in alterations in passive avoidance retention that became apparent over pubertal development. These changes were a function of the gender of the animal.
长期给予腺苷受体拮抗剂会扰乱成年小鼠的空间学习和记忆，新生儿期接触咖啡因会导致小鼠和大鼠出现长期的行为和生化后遗症。因此，我们推测，在被动回避范式中，早期给予咖啡因会对学习和记忆产生潜在影响。在出生后第2至6天，对大鼠不进行处理或通过灌胃给予咖啡因（15 - 20毫克/千克/天）。在28天或70 - 90天时，训练大鼠避开带电网格，并在24小时、72小时和7天后测试记忆保持情况。在28天时，无论性别如何，接触咖啡因的大鼠比对照大鼠需要更多的试验才能达到标准。在这个年龄段，新生儿期处理或性别对记忆保持的影响很小。在70 - 90天时，性别和处理对学习均无影响；然而，在24小时时，性别对记忆保持有显著影响（P < 0.05），在新生儿期接受咖啡因处理的大鼠中更为明显（P < 0.01）。在72小时时，咖啡因对雄性和雌性大鼠记忆保持的影响有所不同。新生儿期接触咖啡因显著改善了雌性大鼠的记忆保持（P < 0.01），并显著降低了雄性大鼠的记忆保持（P < 0.05）。因此，仅限于生命第一周的咖啡因接触导致被动回避记忆保持的改变，这种改变在青春期发育过程中变得明显。这些变化因动物的性别而异。
