Effects of cocaine and cocaine metabolites on mouse developmentin vitro

Toxicology in Vitro : an International Journal Published in Association with BIBRA
E S Hunter, T W Sadler

Abstract

The use of cocaine use has been associated with adverse developmental effects in humans, and cocaine administration produces developmental toxicity in animal models. However, whether the adverse effects produced during organogenesis are due directly to the effects of cocaine or its metabolites remains to be established. This study was therefore undertaken to compare the morphological effects of cocaine and its metabolites, ecgonine, benzoylecgonine (BE) and ecgonine methyl ester (EME) in whole embryo culture (WEC) using early somite stage ICR mice. Cocaine produced a concentration-dependent induction of defects including effects on craniofacial development such as neural tube closure defects (NTDs). Concentrations of cocaine of 51.4 mum or more produced dysmorphogenesis and 100% of the embryos exhibited NTDs at 441 mum. EME also induced defects at concentrations of 400 mum or above. Neither ecgonine nor BE altered embryogenesis at concentrations of 2000 mum or less. The incidence of cocaine-induced NTDs was dependent on the length of exposure to cocaine. At 294 mum, exposures of 3 hr or more were required to alter development when evaluated at the end of a 24-hr culture period. Lower cocaine concentrations required longer expos...Continue Reading

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