长期接触含咖啡因液体的大鼠的行为和身体发育

Butcher R E, Vorhees C V, Wootten V

Fundam Appl Toxicol. 1984 Feb;4(1):1-13. doi: 10.1016/0272-0590(84)90214-8.

Coffee and caffeine solutions were administered as the sole source of fluid to male and female Sprague-Dawley rats (F0) beginning 60 days before breeding and continuing until the litters (F1) from these animals were weaned. Treatments were administered as 100% brewed coffee (COF-100), and a 25% dilution of coffee (COF-25), together with solutions of caffeine in water that paralleled the caffeine content of the coffee groups, 0.056% caffeine (CAF-100) and 0.014% (CAF-25). Controls received measured amounts of plain water (CNL) and another group received vitamin A (40,000 IU/kg) on Days 7-20 of gestation (positive control treatment). During pregnancy all groups receiving COF and CAF consumed significantly more fluid than CNLs. Offspring from the COF-100 and CAF-100 dams were significantly lower in weight than CNLs. No abnormalities of reproductive performance were observed. Of 10 preweaning tests, COF-100 and CAF-100 litters displayed delayed incisor eruption, delayed swimming development, and altered activity. On 7 postweaning measures, these groups showed decreased running wheel activity and increased open-field ambulation and/or defecation. The CAF-25 group, by contrast, showed an increase in running wheel activity. Vitamin A (Vit-A) offspring showed multiple effects, including delayed incisor eruption, increased pre- and postweaning open-field activity, and reduced running wheel activity. COF and CAF produced effects on tests for psychoteratogenesis that appear consistent with the morphological consequences (delayed development) known to be associated with pre- and neonatal administration of caffeine, alone or in coffee, at high doses. The data indicate that most of the behavioral effects observed from caffeine exposure were consistent with the expected effects of concurrent administration of this agent, while the postweaning exposure effects suggest a longer-term change in activity. No effects of caffeine were found, however, on measures of learning, memory, or motoric functioning.

从繁殖前60天开始，直至这些动物的幼崽（F1）断奶，咖啡和咖啡因溶液作为唯一的液体来源给予雄性和雌性斯普拉格-道利大鼠（F0）。处理方式包括100%煮制咖啡（COF-100）、咖啡25%稀释液（COF-25），以及与咖啡组咖啡因含量相当的咖啡因水溶液，即0.056%咖啡因（CAF-100）和0.014%（CAF-25）。对照组给予定量的纯水（CNL），另一组在妊娠第7至20天给予维生素A（40,000 IU/kg）（阳性对照处理）。在孕期，所有接受COF和CAF的组比CNL组消耗的液体显著更多。来自COF-100和CAF-100母鼠的后代体重显著低于CNL组。未观察到生殖性能异常。在10项断奶前测试中，COF-100和CAF-100窝幼崽出现切牙萌出延迟、游泳发育延迟和活动改变。在7项断奶后测量中，这些组显示跑轮活动减少，旷场行走和/或排便增加。相比之下，CAF-25组跑轮活动增加。维生素A（Vit-A）组后代出现多种影响，包括切牙萌出延迟、断奶前后旷场活动增加以及跑轮活动减少。COF和CAF对精神致畸测试产生的影响，似乎与已知的单独或与咖啡一起高剂量给予咖啡因在产前和新生儿期给药所导致的形态学后果（发育延迟）一致。数据表明，咖啡因暴露观察到的大多数行为影响与同时给予该药物的预期效果一致，而断奶后暴露影响表明活动存在长期变化。然而，未发现咖啡因对学习、记忆或运动功能测量有影响。