c-fos and cleaved caspase-3 expression after perinatal exposure to ethanol, cocaine, or the combination of both drugs

Poly-drug abuse during pregnancy is a major public health concern. The combined effects of cocaine and ethanol may be more injurious to the fetal nervous system than either drug alone. In order to identify areas of the brain vulnerable to concuffent exposure, we examined the expression of the immediate-early gene (IEG), c-fos, and cleaved caspase-3, the 'executioner' caspase in apoptosis. Pregnant rats were treated with either ethanol diet, cocaine binge, or both. At birth, the brains of fetuses exposed to cocaine exhibited an increase in Fos immunoreactivity in many brain regions. Prenatal exposure to ethanol did not increase Fos expression above that observed in control rats at early points after birth. However, Fos expression at 24 h after birth was higher after ethanol diet treatment in several brain regions, such as the amygdala, ventromedial hypothalamus, and medial thalamus. Only in the striatum did the combination of ethanol and cocaine cause greater Fos expression than either prenatal cocaine or ethanol alone. Increased cleaved caspase-3 expression was observed at the 24-h time point for both ethanol- and cocaine-exposed brains, most notably in the septum, retrosplenial cortex, and the hippocampus. Concurrent ethanol and cocaine exposure did not elevate cleaved caspase-3 expression beyond that of either drug alone. Analysis of the extent of c-fos and caspase-3 induction did not indicate a consistent relationship of expression in any of the drug treatment groups nor in any brain region. These results indicate that both prenatal cocaine and prenatal ethanol exposure increase Fos and cleaved caspase-3 expression in the developing brain in a time- and region-dependent manner,, but that the combination of low-dose, chronic ethanol, and binge cocaine does not cause greater apoptosis. (C) 2003 Elsevier B.V All rights reserved.