Weese-Mayer D E, Klemka-Walden L M, Chan M K, Gingras J L
Department of Pediatrics, Rush Medical College, Rush University, Chicago, Ill.
Dev Pharmacol Ther. 1991;16(4):221-30.
Prenatal cocaine (CC) exposure may result in increased fetal loss, growth retardation, altered neurodevelopment, and sudden infant death syndrome (SIDS). We sought to establish an animal model for prenatal cocaine exposure which (1) would allow us to distinguish the direct effects from the indirect and nutritional effects of the drug, and (2) might be used to address questions of cocaine's toxicity, specifically to the developing respiratory control system. The study design included 38 New Zealand White rabbit does among CC, pair-fed (PF), and free-fed (FF) groups. Miniosmotic pumps were implanted in each doe on day 10 of timed gestation providing continuous subcutaneous administration of either 30 mg/kg/day of cocaine HCl in H2O (CC) or sterile H2O alone (PF and FF). Mean (SEM) plasma cocaine concentration was 1.71 +/- 0.21 mumol/l (519.4 +/- 64.4 ng/ml). Pregnancy outcome compared for incidence of stillbirth, maternal death, spontaneous abortion, and gross malformation among 211 pups was significant only for increased stillbirths among CC pups (18%, p less than 0.04) as compared to PF (6%) and FF pups (7%). External and renal malformation and postnatal weight, crown-rump length, and snout-occiput head circumference for pups aged 4 and 5 days of age did not differ among groups. The direct effects of prenatal cocaine evaluated in our model do not reproduce the altered perinatal outcome observed among humans. However, our results do not determine if physiologic function has been altered. Investigation of the physiologic and pathologic abnormalities that are relevant to this human condition, specifically to the developing respiratory control system, should add clarity to the mechanism of action of cocaine during pregnancy.
产前接触可卡因（CC）可能会导致胎儿丢失增加、生长发育迟缓、神经发育改变以及婴儿猝死综合征（SIDS）。我们试图建立一种产前接触可卡因的动物模型，该模型（1）能让我们区分药物的直接作用与间接和营养作用，（2）可用于解决可卡因毒性问题，特别是对发育中的呼吸控制系统的毒性问题。研究设计包括将38只新西兰白兔母兔分为CC组、配对喂养（PF）组和自由喂养（FF）组。在妊娠第10天给每只母兔植入微型渗透泵，持续皮下注射30mg/kg/天的盐酸可卡因水溶液（CC组）或仅注射无菌水（PF组和FF组）。血浆可卡因平均（标准误）浓度为1.71±0.21μmol/L（519.4±64.4ng/ml）。在211只幼崽中比较妊娠结局，包括死产、母体死亡、自然流产和严重畸形的发生率，与PF组（6%）和FF组（7%）相比，CC组幼崽的死产率显著增加（18%，p<0.04）。4日龄和5日龄幼崽的外部和肾脏畸形以及出生后体重、顶臀长度和鼻枕头围在各组之间没有差异。在我们的模型中评估的产前可卡因的直接作用并未重现人类中观察到的围产期结局改变。然而，我们的结果并未确定生理功能是否已改变。对与这种人类状况相关的生理和病理异常进行研究，特别是对发育中的呼吸控制系统进行研究，应该会更清楚地了解可卡因在孕期的作用机制。
