Shepanek N A, Smith R F, Anderson L A, Medici C N
George Mason University, Fairfax, VA 22030-4444, USA.
Pharmacol Biochem Behav. 1995 Mar;50(3):313-9. doi: 10.1016/0091-3057(94)00232-8.
Pregnant Long-Evans hooded rats were dosed with 1, 5, or 10 mg/kg per day naloxone from gestational day 7 (GD7) through GD20. The control groups included both uninjected animals and injected animals pairfed to the 10-mg dose animals. At birth, all litters were culled to four males and four females, and fostered to undosed surrogate dams. Prenatal naloxone exposure produced changes in body weight development, pain sensitivity, and motor behavior in the offspring. Five and 10 mg/kg naloxone increased adult body weights in females only, as did the pairfeeding condition. The 10 mg/kg naloxone altered pain sensitivity (in males only) as measured by the tail flick test. Animals in the 1 mg/kg dose condition habituated more rapidly than uninjected (UN) subjects in the open field, and showed less activity than UNs as they matured. Bar pressing rates were reduced in the 10 mg/kg dose males in a visual discrimination task, while 10 mg/kg males and females showed reduced bar pressing rates on differential reinforcement of low rates of responding (DRL). These findings confirm that prenatal exposure to naloxone alters some aspects of neurobehavioral development in the rat, and are consistent with the hypothesis that 1 mg/kg prenatally may increase opiate function in offspring, while 10 mg/kg prenatally may decrease opiate functioning in the offspring.
从妊娠第7天（GD7）至GD20，对怀孕的Long-Evans有帽大鼠每天给予1、5或10mg/kg的纳洛酮。对照组包括未注射的动物以及与10mg剂量组动物配对饲养的注射动物。出生时，所有窝仔均挑选出4只雄性和4只雌性，并寄养给未给药的代孕母鼠。产前暴露于纳洛酮会使后代的体重发育、疼痛敏感性和运动行为发生变化。5mg/kg和10mg/kg的纳洛酮仅增加了雌性成年后的体重，配对饲养条件下也是如此。10mg/kg的纳洛酮改变了（仅在雄性中）通过甩尾试验测量的疼痛敏感性。1mg/kg剂量组的动物在旷场中比未注射（UN）的动物更快地产生习惯化，并且随着它们的成熟，其活动量比未注射组少。在视觉辨别任务中，10mg/kg剂量组的雄性动物的压杆率降低，而10mg/kg剂量组的雄性和雌性在低反应率差异强化（DRL）任务中的压杆率均降低。这些发现证实，产前暴露于纳洛酮会改变大鼠神经行为发育的某些方面，并且与以下假设一致：产前1mg/kg可能会增加后代的阿片类药物功能，而产前10mg/kg可能会降低后代的阿片类药物功能。
