Finnell R H, Toloyan S, van Waes M, Kalivas P W
Department of Veterinary and Comparative Anatomy, College of Veterinary Medicine, Washington State University, Pullman 99164.
Toxicol Appl Pharmacol. 1990 Apr;103(2):228-37. doi: 10.1016/0041-008x(90)90226-k.
The current dramatic increase in illicit cocaine use by individuals during their reproductive years has heightened concerns over the possible adverse effects of maternal cocaine abuse during pregnancy. To address such concerns, the teratogenic effects of cocaine hydrochloride were investigated in two inbred mouse strains (SWV and DBA/2J). The drug was administered on either Gestational Days 6-8 or 8-10 by intraperitoneal injection, and the progeny examined on Gestational Day 18. While treatment with increasing concentrations of the drug did not adversely affect the rates of implantation, resorption, maternal weight gain, or fetal weights, there was a dose-related effect on the frequency of congenital malformations. This was consistently observed in both mouse strains. The types of congenital defects observed in the mouse fetuses bore a striking similarity to those reported in the clinical literature, including cardiovascular defects, limb abnormalities, and genitourinary malformations.
当前,处于生育年龄的个体非法使用可卡因的情况急剧增加,这引发了人们对孕期母亲滥用可卡因可能产生的不良影响的更多关注。为了解决这些担忧,研究人员在两种近交小鼠品系(SWV和DBA/2J)中研究了盐酸可卡因的致畸作用。通过腹腔注射在妊娠第6 - 8天或8 - 10天给予该药物,并在妊娠第18天检查后代。虽然用浓度不断增加的药物进行治疗并未对着床率、吸收率、母体体重增加或胎儿体重产生不利影响,但对先天性畸形的发生率存在剂量相关效应。在两种小鼠品系中均一致观察到这一点。在小鼠胎儿中观察到的先天性缺陷类型与临床文献中报道的缺陷类型极为相似,包括心血管缺陷、肢体异常和泌尿生殖系统畸形。